Instrument for analyzing biological samples and reagents

ABSTRACT

An instrument for processing a biological sample includes a chassis. Connected to the chassis is a tape path along which a tape with a matrix of wells can be automatically advanced through the instrument, a dispensing assembly for dispensing the biological sample and a reagent into the matrix of wells of the tape to form a biological sample and reagent mixture, a sealing assembly for sealing the biological sample and reagent mixture in the tape, and an amplification and detection assembly for detecting a signal from the biological sample and reagent mixture in the matrix of wells in the tape.

BACKGROUND

The present invention relates to an instrument for analyzing biologicalsamples, and in particular, to an all-in-one instrument that is capableof dispensing, amplifying, and analyzing biological samples.

A biological sample and reagent mixture can undergo amplification andanalysis to detect the presence of an analyte in the mixture.Historically, biological sample and reagent mixtures were amplified andanalyzed for research applications, including DNA sequencing, genemapping, and DNA cloning, among other things. Biological sample andreagent mixture amplification and analysis is becoming increasinglypopular and innovative uses are constantly being discovered, includingmedical applications, infectious disease applications, and forensicapplications. With the increase in popularity of biological sample andreagent mixture amplification and analysis comes a need for moreadvanced equipment.

Equipment that is currently available to prepare, amplify, and analyze abiological sample and reagent mixture includes laboratory equipment,handheld devices, and lab-on-a-chip devices. Handheld devices andlab-on-a-chip devices are not capable of testing a large number ofbiological sample and reagent mixtures at the same time, thus makingthem unsuitable for many applications. To amplify and analyze a largenumber of biological sample and reagent mixtures, laboratory equipmentmust be used. Laboratory equipment typically involves many separatepieces of equipment, where each piece of equipment is used for adifferent purpose. For instance, a first piece of equipment can be usedto prepare the biological sample and reagent mixture, a second piece ofequipment can be used to amplify the biological sample and reagentmixture, and a third piece of equipment can be used to analyze thebiological sample and reagent mixture. The different pieces of equipmenttake up a lot of space in laboratories and it can be costly to acquireall of the equipment needed to prepare, amplify, and analyze thebiological sample and reagent mixture. Further, the amount of biologicalsample and the amount of reagent needed to analyze the biological sampleand reagent mixture using existing laboratory equipment can be expensivedue to the cost of acquiring the biological sample and the reagent.

SUMMARY

An instrument for processing a biological sample includes a chassis.Connected to the chassis is a tape path along which a tape with a matrixof wells can be automatically advanced through the instrument, adispensing assembly for dispensing the biological sample and a reagentinto the matrix of wells of the tape to form a biological sample andreagent mixture, a sealing assembly for sealing the biological sampleand reagent mixture in the tape, and an amplification and detectionassembly for detecting a signal from the biological sample and reagentmixture in the matrix of wells in the tape.

An instrument for amplifying and analyzing a biological sample and areagent includes a path extending through the device for advancing atape containing a plurality of wells through the instrument. Positionedalong the path and downstream of an entrance to the path is a dispensingand sealing station with a dispensing assembly positioned adjacent tothe dispensing and sealing station to dispense a biological sample and areagent into the plurality of wells in the tape to form a biologicalsample and reagent mixture, and a tape sealing assembly positionedadjacent to the dispensing and sealing station to seal the biologicalsample and reagent mixture in the plurality of wells in the tape.Positioned along the path and downstream of the dispensing and sealingstation is a holding station with a thermal unit positioned below theholding station to heat or cool the biological sample and reagentmixture in the plurality of wells in the tape. Positioned along the pathand downstream of the holding station is an amplification and detectionstation with a thermal unit to amplify the biological sample and reagentmixture, and a detection unit to detect a signal from the biologicalsample and reagent mixture.

An instrument for amplifying and detecting a biological sample includesa plate rack that is capable of holding one or more plates; a platestacker to lift a plate out of the plate rack; a plate shuttle with aplatform on which the plate stacker can place the plate from the platerack, wherein the plate shuttle can position the platform for aspiratingor dispensing; a plate deck on which a plate can be placed; a dispensingassembly with a first plurality of tips and a second plurality of tips,wherein the dispensing assembly can dispense a biological sample and areagent into the plurality of wells on the tape to form a biologicalsample and reagent mixture; a path extending through the instrumentalong which the tape is advanced through the instrument; a tape sealerthat seals the plurality of wells in the tape; a thermal unit that heatsthe biological sample and reagent mixture in the plurality of wells inthe tape; a heated pressure chamber that pressurizes an area over thetape; and a detection device that detects a signal from the biologicalsample and reagent mixture in the plurality of wells in the tape.

An instrument for processing a biological sample includes a tape with aplurality of wells, wherein the tape has a first matrix of wells and asecond matrix of wells offset from and interlaced with the first matrixof wells. The instrument also includes a tape path extending through theinstrument along which the tape with the plurality of wells can beautomatically advanced. The instrument further includes a dispensingassembly for dispensing the biological sample and a reagent into theplurality of wells of the tape, wherein the dispensing assembly candispense the biological sample or the reagent into the first matrix ofwells and reposition to dispense the biological sample or the reagentinto the second matrix of wells.

A method of analyzing a biological sample and reagent mixture in aninstrument includes automatically advancing a tape with a matrix ofwells to a first position on a tape path in the instrument using a tapeinfeed and a drive mechanism positioned along the tape path;automatically advancing the tape to a second position on the tape pathin the instrument using the drive mechanism positioned along the tapepath; dispensing a biological sample into the matrix of wells in thetape with a dispensing assembly when the tape is positioned at thesecond position of the tape path; dispensing a reagent into the matrixof wells in the tape with a dispensing assembly when the tape ispositioned at the second position of the tape path, wherein a biologicalsample and reagent mixture is formed; sealing a seal over the matrix ofwells in the tape with a tape sealer when the tape is positioned at thesecond position; automatically advancing the tape to a third position onthe tape path in the instrument using the drive mechanism positionedalong the tape path; automatically advancing the tape to a fourthposition on the tape path in the instrument using the drive mechanismpositioned along the tape path; amplifying the biological sample andreagent mixture at the fourth position of the tape path; and detecting asignal from the biological sample and reagent mixture using a camerapositioned above the fourth position of the tape path.

A tape path assembly for an instrument for processing a biologicalsample includes a tape path having a front end, a back end, a firstposition downstream of the front end, a second position downstream ofthe first position, a third position downstream of the second position,and a fourth position between the third position and the back end. Thetape path assembly also includes a tape infeed attached to the front endthat automatically advances a tape with a matrix of wells to the firstposition of the tape path, and a drive mechanism that advances the tapealong the tape path.

An instrument for processing a biological sample includes a tape pathalong which a tape with a matrix of wells can be automatically advancedthrough the instrument; a dispensing system for dispensing thebiological sample and a reagent into the matrix of wells of the tape toform a biological sample and reagent mixture; a sealing system forsealing the biological sample and reagent mixture in the tape; and anamplification and detection system for detecting a signal from thebiological sample in the matrix of wells in the tape, wherein theamplification and detection system includes a thermal unit positioned onthe tape path that is capable of controlling the temperature of thebiological sample and reagent mixture in the matrix of wells of thetape.

An apparatus for heating a plurality of wells of a tape includes a firstlayer with cavities that are capable of receiving wells of a tape, asecond layer attached to a bottom side of the first layer, and a heatpump positioned on a bottom side of the second layer, wherein the heatpump is positioned so that heat can be exchanged between the heat pumpand a biological sample and reagent mixture in the wells on the tapethrough the second layer and the first layer.

An apparatus includes a tape with a matrix of wells, a thermal unitpositioned below the tape with a matrix of wells, and a chamberpositioned on top of the tape with a matrix of wells. The chamberincludes a housing and a glass cover plate, wherein the housing and theglass cover plate form an enclosed space above the matrix of wells ofthe tape.

An instrument for processing a biological sample includes a tape pathalong which a tape with a matrix of wells can be automatically advancedthrough the instrument. The instrument further includes a plate stackerwith an arm that can rotate around and move vertically on a z-axis. Thearm is configured to pick a plate out of a plate rack and place theplate on a plate shuttle. The instrument further includes a dispensingsystem for dispensing the biological sample and a reagent into thematrix of wells of the tape to form a biological sample and reagentmixture, a sealing system for sealing the biological sample and reagentmixture in the tape, and an amplification and detection system fordetecting a signal from the biological sample and reagent mixture in thematrix of wells in the tape.

A plate stacker assembly includes a plate rack that includes a pluralityof nests attached to a frame, wherein each of the plurality of nests hasa plurality of corner supports that are capable of supporting a plate.The plate stacker assembly also includes a plate shuttle that includes anest attached to a support structure, wherein the nest has a pluralityof corner supports that are capable of supporting one plate. The platestacker assembly further includes a spatula that is capable of picking aplate off of one of the plurality of nests in the plate stacker andplacing it on the nest in the plate shuttle, wherein the spatula has asupport member that is capable of supporting a plate and notches is eachcorner of the support member that correspond to the location of thecorner supports on the nests in the plate stacker and the plate shuttle.

A method for moving a plate in an instrument includes picking a plateoff of a nest of a plate rack using a spatula attached to an arm of aplate stacker; rotating the arm of the plate stacker around a z-axis;moving the arm of the plate stacker in a vertical direction along thez-axis; and placing the plate on a nest of a plate shuttle.

A tape sealing assembly includes a spool holder for holding a seal web,a peel plate located downstream of the spool holder, and a backertake-up mechanism downstream of the peel plate for advancing the sealweb across the peel plate. The tape sealing assembly also includes anapplicator positioned above the peel plate for peeling a seal from abacker of the seal web and applying the seal to a surface.

A dispensing assembly includes a gantry with an x-axis track and ay-axis track. The y-axis track of the gantry is configured to move alongthe x-axis track of the gantry. The dispensing assembly further includesa dispensing head attached to the y-axis track of the gantry below they-axis track of the gantry. The dispensing head includes a contactdispensing unit and a non-contact dispensing unit with a jet tip fordispensing a liquid. The dispensing assembly further includes adispensing enclosure attached to the y-axis track of the gantry on topof the y-axis track of the gantry. The dispensing enclosure includes apressure reservoir. A tube connects the jet tip of the non-contactdispensing unit to the pressure reservoir of the dispensing enclosure.The contact dispensing unit is attached to the y-axis track of thegantry with a first z-axis track, and the non-contact dispensing unit isattached to the contact dispensing unit with a second z-axis track.

A method of operating a dispensing assembly includes moving a dispensinghead along an x-axis track and a y-axis track of a gantry into a firstaspiration position, aspirating a first liquid with a pipette tip of acontact dispensing unit of the dispensing head, moving the dispensinghead along the x-axis track and the y-axis track of the gantry into asecond aspiration position, aspirating a second liquid with a jet tip ofa non-contact dispensing unit of the dispensing head, moving thedispensing head along the x-axis track and the y-axis track of thegantry into a first dispensing position, dispensing the first liquidinto a well of a tape with a matrix of wells with the pipette tip of thecontact dispensing unit, moving the dispensing head along the x-axistrack and the y-axis track of the gantry into a second dispensingposition, and dispensing the second liquid into a well of the tape witha matrix of wells with the jet tip of the non-contact dispensing unit.The contact dispensing unit of the dispensing head extends and retractsalong a first z-axis track connected to the y-axis track of the gantry,and the non-contact dispensing unit of the dispensing head extends andretracts along a second z-axis track connected to the contact dispensingunit.

BRIEF DESCRIPTION OF THE DRAWINGS

Overall Instrument

FIG. 1A is an isometric view of a cart top instrument for amplifying andanalyzing a biological sample and reagent mixture.

FIG. 1B is a side view of the instrument seen in FIG. 1A.

FIG. 1C is a top plan view of the instrument seen in FIG. 1A.

FIG. 1D is an exploded view of the instrument seen in FIG. 1A.

FIG. 1E is a front isometric view of a tape path assembly that runsthrough the instrument seen in FIG. 1A.

FIG. 1F is a back perspective view of the tape path assembly as seen inFIG. 1E.

FIG. 2A is an isometric view of the instrument.

FIGS. 2B-2D are perspective views of the instrument.

FIGS. 2E-2F are back perspective views of the tape path assembly thatruns through the instrument.

FIG. 3A is a top plan view of a thermal management system in theinstrument.

FIG. 3B is a perspective view of the thermal management system seen inFIG. 3A.

FIG. 3C is a schematic view of the thermal management system seen inFIGS. 3A and 3B.

FIG. 4A is a top plan view of a tape with a plurality of wells.

FIG. 4B is a schematic view of the tape seen in FIG. 4A with a firstplurality of wells and a second plurality of wells.

Plate Stacker Assembly

FIG. 5A is an isometric view of a plate stacker assembly in theinstrument.

FIG. 5B is a top cut away view of the plate stacker assembly in theinstrument.

FIG. 5C is an isometric view of the plate stacker assembly.

FIG. 6A is an isometric view of a plate rack.

FIG. 6B is a top plan view of a nest of the plate rack.

FIG. 7A is a perspective view of a plate stacker.

FIG. 7B is a perspective view of a portion of the plate stacker and aportion of the plate rack.

7C is an isometric view of a portion of the plate stacker seen in FIG.7A.

FIG. 8A is an isometric view of a plate shuttle.

FIG. 8B is an isometric view of a plate shuttle in the instrument.

FIG. 9A is an isometric view of the plate rack and the plate stackerwhen a spatula is in a home position.

FIG. 9B is an isometric view of the plate rack and the plate stackerwhen the spatula has been moved from the home position.

FIG. 9C is an isometric view of the plate rack and the plate stackerwhen the spatula is positioned to pick a plate.

FIG. 9D is a perspective view of the plate stacker and the plate shuttlewhen the spatula has placed the plate in a nest of the plate shuttle.

Deck Plate Assembly

FIG. 10 is an isometric view of a deck plate assembly in the instrument.

FIG. 11A is a partially transparent isometric view of a deck platestation of the deck plate assembly.

FIGS. 11B-11D are perspective views of the deck plate station seen inFIG. 11A.

FIGS. 12A and 12B are partially transparent perspective views of thedeck plate station.

FIG. 13 is a partially transparent perspective view from underneath thedeck plate station.

FIG. 14 is a bottom view of the deck plate station.

FIG. 15 is a partially transparent side view of the deck plate station.

FIG. 16 is a side view of the deck plate station within the instrument.

Tape Path Assembly

FIG. 17A is an isometric view of a tape path assembly in the instrument.

FIG. 17B is a front isometric view of the tape path assembly.

FIG. 18A is a front isometric view of the tape path assembly with a tapeinfeed in a retracted position.

FIG. 18B is a front isometric view of the tape path assembly seen inFIG. 19A with the tape infeed in an extended position.

FIG. 19A is a back perspective view of the tape path assembly with adrive mechanism.

FIG. 19B is a back isometric view of the drive mechanism.

FIG. 19C is a perspective view of a roller on the tape path assembly.

FIG. 20A is a front plan view of a tape infeed on the tape pathassembly.

FIG. 20B is a front isometric view of the tape infeed on the tape pathassembly.

FIG. 21A is a back perspective view of a tape cutter on the tape pathassembly.

FIG. 21B is a plan view of a front side of the tape cutter having theblade in a retracted position.

FIG. 21C is a plan view of a front side of the tape cutter having theblade in an extended position.

FIG. 21D is a plan view at an entrance of the tape path assembly withthe tape cutter having the blade in a retracted position.

FIG. 21E is a partially transparent plan view at an entrance of the tapepath assembly with the tape cutter having the blade in an extendedposition.

FIG. 22A is a partially transparent front perspective view of a liftmechanism.

FIG. 22B is a plan view of the lift mechanism.

FIG. 23A is a front plan view of the lift mechanism on the tape pathassembly in a retracted position.

FIG. 23B is a front plan view of the lift mechanism on the tape pathassembly in an extended position.

FIG. 24 is a front perspective view of thermal units on the tape pathassembly.

FIG. 25 is a bottom view of fluid paths on the tape path assembly.

FIG. 26A is a partially transparent side view of a retractable holddown.

FIG. 26B is a back perspective view of the retractable hold down on thetape path assembly with the retractable hold down in a retractedposition.

FIG. 26C is a back perspective view of the retractable hold down on thetape path assembly with the retractable hold down in an extendedposition.

FIG. 27 is a perspective view of a rewind assembly that can accumulateprocessed tape leaving the tape path assembly.

Dispensing Assembly

FIG. 28 is an isometric view of a dispensing assembly in the instrument.

FIG. 29 is a schematic diagram of the dispensing assembly seen in FIG.28.

FIG. 30 is a perspective view of the y-axis gantry of the dispensingassembly seen in FIG. 28.

FIGS. 31A-31B are isometric views of the dispensing head of thedispensing assembly seen in FIG. 28.

FIG. 31C is a partially transparent perspective view of two z-axes ofthe dispensing head seen in FIGS. 31A-31B.

FIG. 32A is a transparent isometric view of the dispensing enclosure ofthe dispensing assembly seen in FIG. 28.

FIG. 32B is a transparent perspective view of the dispensing enclosureof the dispensing assembly seen in FIG. 28.

FIG. 33 is a schematic diagram of non-contact dispensing components ofthe dispensing enclosure and the dispensing head seen in FIGS. 31A-31Cand 32A-32B.

Tape Sealing Assembly

FIG. 34A is an isometric view of a tape sealing assembly in theinstrument.

FIG. 34B is a perspective view of a seal web.

FIG. 35 is a perspective view of the tape sealing assembly positionedadjacent to a tape path assembly.

FIG. 36A is a top view of the tape sealing assembly within theinstrument.

FIGS. 36B-36C are perspective views of the tape sealing assembly.

FIG. 37A is an isometric view of a portion of the tape sealing assembly.

FIG. 37B is a side view of the tape sealing assembly with a seal webthreading path.

FIG. 38A is a perspective view of a backer take-up mechanism of the tapesealing assembly.

FIG. 38B is a side view of the backer taker-up mechanism in FIG. 38Awith friction roller in a closed position

FIG. 38C is a side view of the backer taker-up mechanism in FIG. 38Awith friction roller in an open position

FIG. 39A is a cross-sectional view of a locking mechanism of the tapesealing assembly in an unlocked position.

FIG. 39B is a cross-sectional view of a locking mechanism of the tapesealing assembly in a locked position.

FIG. 40 is a partially transparent perspective view of an applicator ofthe tape sealing assembly.

FIG. 41 is a bottom view of a pad of the applicator.

FIGS. 42A-42B are partially transparent perspective views of a portionof the tape sealing assembly removing a seal from a backer of the sealweb.

FIGS. 43A-43B are side views of the tape sealing assembly applying aseal to a tape on the tape path assembly.

Thermal Unit and Heated Pressure Chamber

FIG. 44 is an isometric view of a tape path assembly that runs throughan instrument.

FIG. 45A is a perspective view of a thermal unit and a heated pressurechamber, with the heated pressure chamber in a closed position.

FIG. 45B is a perspective view of a thermal unit and a heated pressurechamber, with the heated pressure chamber in a closed position.

FIG. 45C is an exploded view of the thermal unit and the heated pressurechamber.

FIG. 45D is an exploded view of thermal unit.

FIG. 45E is an exploded view of the heated pressure chamber.

FIG. 46A is a perspective view of the thermal unit.

FIG. 46B is a perspective view of the bottom of the thermal unit.

FIG. 46C is a top view of the thermal unit.

FIG. 46D is an isometric view of an array of tape on the thermal unit.

FIG. 47A is a cross-sectional side view of the thermal unit.

FIG. 47B is a cut-away cross-sectional side view of the thermal unit.

FIG. 47C is a schematic view of a cross-section of the thermal unit.

FIG. 48 is a top plan see-through view of a top side of the thermalunit.

FIG. 49 is a bottom plan see-through view of the thermal unit.

FIG. 50 is a cross-sectional view of the heated pressure chamber andthermal unit.

FIG. 51 is an isometric view of the heated pressure chamber.

FIG. 52 is a top view of the heated pressure chamber.

Alternative Embodiments of the Overall Instrument

FIG. 53A is a schematic view of an alternative embodiment of theinstrument seen in FIGS. 1A-52.

FIG. 53B is a schematic view of an alternative embodiment of theinstrument seen in FIGS. 1A-52.

DETAILED DESCRIPTION

In general, the present disclosure relates to an instrument foranalyzing biological sample and reagent mixtures. The instrument is anall-in-one instrument that is capable of dispensing, amplifying, andanalyzing biological samples and reagents in a compact design. A tapecontaining a plurality of wells is automatically advanced through theinstrument along a tape path assembly. The tape path assembly includes afirst position, a second position, a third position, and a fourthposition. At the first position, the tape can be cut so that a tapesegment with a single array of wells proceeds through the instrument.Alternatively, the tape can advance through the first position to thesecond position without being cut. Further, the tape can advance withoutbeing cut until any number of arrays of wells have passed through thefirst position and the tape can then be cut. At the second position, abiological sample and a reagent are dispensed into the plurality ofwells in the tape with a dispensing assembly to form a biological sampleand reagent mixture. After the biological sample and the reagent aredispensed into the tape, a tape sealing assembly seals the tape with aseal, such as an optically clear cover seal. The tape then advances tothe third position. At the third position, the tape containing thebiological sample and reagent mixture can either be cooled to preventthe biological sample and reagent mixture from undergoing a chemicalreaction or heated to incubate the biological sample and reagentmixture. The tape will then advance to the fourth position. At thefourth position, the biological sample and reagent mixture in theplurality of wells in the tape can be amplified and analyzed with adetection assembly. The all-in-one instrument is capable of amplifyingnucleic acids in the biological sample and reagent mixture by thermalcycling the biological sample and reagent mixture (polymerase chainreaction) or by heating the biological sample and reagent mixture at aconstant temperature (isothermal amplification). As the tape advancesthrough the system, the second position, the third position, and thefourth position can function at the same time to allow the instrument tocontinuously dispense, amplify, and analyze the biological sample andreagent mixture in the tape.

The all-in-one instrument is advantageous, as it performs all of thefunctions needed to dispense, amplify, and analyze a biological sampleand reagent mixture without the need for human intervention. A user cansimply select parameters for the instrument and position a biologicalsample and a reagent in the instrument. The instrument can then aspiratethe biological sample and the reagent, automatically advance tapethrough the instrument, dispense the biological sample and the reagentinto the tape, and amplify and analyze the biological sample and reagentmixture in the tape. The instrument is further advantageous, as it has acompact design that supports all of the components necessary forperforming the functions of the instrument on a single chassis. Further,the functions provided in the instrument allow the instrument to be usedfor large scale testing with high-throughput or small scale testing withlow-throughput. The compact design, efficiency, and versatility of theinstrument allow the instrument to be used in a large variety ofsettings and for a large number of different applications.

Overall Instrument

FIG. 1A is an isometric view of instrument 100 mounted on cart assembly101. FIG. 1B is a side view of instrument 100 on cart assembly 101 seenin FIG. 1A. FIG. 1C is a top plan view of instrument 100. FIG. 1D is anexploded view of instrument 100. FIG. 1E is a front isometric view oftape path assembly 118 that runs through instrument 100. FIG. 1F is aback perspective view of tape path assembly 118 as seen in FIG. 1D.Instrument 100 is mounted on cart assembly 101 and includes chassis 102,enclosure 103 (removed for clarity in subsequent figures), tape 104 (asshown in FIGS. 1E-1F), seal 106 (as shown in FIGS. 1E-1F), plate stackerassembly 110, deck plate assembly 112, dispensing assembly 114, washassembly 116, tape path assembly 118, tape sealing assembly 120,detection assembly 122 (as shown in FIGS. 1C-1D), and electronicassembly 124. Enclosure 103 provides a controlled environment for areaction to take place in instrument 100. Enclosure 103 includes intakefilters, an exhaust filter, and an exhaust blower in order to controlair quality within instrument 100.

Also mounted on cart assembly 101 is rewind assembly 108. Rewindassembly 108 is aligned with tape path assembly 118. Cart assembly 101includes a bleach reservoir, a waste tank with an exhaust filter and anactivated carbon filter for wash assembly 116. Cart assembly 101 alsoincludes two water tanks for providing system fluid to dispensingassembly 114 and wash assembly 116. As shown in FIGS. 1E-1F, tape pathassembly 118 includes first position 130, second position 132, thirdposition 134, and fourth position 136.

Instrument 100 can be used to dispense, amplify, and analyze abiological sample and reagent mixture. Instrument 100 includes aplurality of assemblies that are all positioned on chassis 102. Tape 104is advanced through instrument 100. Tape 104 has a plurality of wellsthat can receive a biological sample and a reagent for amplification andanalysis. The plurality of wells on tape 104 are arranged in arrays, sothat each array is spaced apart from adjacent arrays. In the embodimentshown, tape 104 is a white and opaque tape. In alternate embodiments,tape 104 can be black, white, or gray and transparent, semi-transparent,or opaque. Tape 104 can be made of a plastic material such aspolypropylene or another suitable material such as metal foil.

As tape 104 advances through instrument 100, the plurality of assembliesin instrument 100 will interact with tape 104. The assemblies that areincluded on instrument 100 are plate stacker assembly 110, deck plateassembly 112, dispensing assembly 114, wash assembly 116, tape pathassembly 118, tape sealing assembly 120, detection assembly 122, andelectronic assembly 124. The plurality of assemblies are positioned onchassis 102 of instrument 100 to minimize the size of chassis 102 andinstrument 100. Minimizing the size of chassis 102, and thus instrument100, allows instrument 100 to have a compact design.

Each assembly in instrument 100 performs a function related todispensing, amplifying, and/or analyzing a biological sample and reagentmixture so that instrument 100 can operate as an all-in-one assembly.Plate stacker assembly 110 is capable of receiving and moving platescontaining a biological sample and/or a reagent in instrument 100. Deckplate assembly 112 is capable of receiving plates containing abiological sample and/or a reagent. Dispensing assembly 114 can aspiratea biological sample and/or a reagent from a plate in plate stackerassembly 110 and dispense the biological sample and/or the reagent intotape 104 in instrument 100. Dispensing assembly 114 can also aspirate abiological sample and/or a reagent from a plate in deck plate assembly112 and dispense the biological sample and/or the reagent into tape 104in instrument 100. Further, dispensing assembly 114 can aspirate abiological sample and/or reagent from any of a plate in plate stackerassembly 110, a plate in deck plate assembly 112, or tape 104, and candispense the biological sample and/or reagent into a plate in platestacker assembly 110, a plate in deck plate assembly 112, or tape 104.Wash assembly 116 is used to clean dispensing assembly 114 before and/orafter dispensing assembly 114 is used to dispense the biological sampleand the reagent into tape 104.

Tape 104 advances along tape path assembly 118 through instrument 100.Tape path assembly 118 extends through instrument 100 and provides apath along which tape 104 can advance. Tape path assembly 118 includesfirst position 130, second position 132, third position 134, and fourthposition 136. Different functions are completed at each position alongtape path assembly 118. At first position 130, tape 104 can be cut tosingulate tape 104 into a tape segment with a single array of wells.Alternatively, tape 104 can advance as a web through first position 130without being cut, or tape 104 can be cut after any number of arrays ofwells have passed through first position 130. At second position 132,dispensing assembly 114 dispenses the biological sample and the reagentinto tape 104 to form a biological sample and reagent mixture. Further,tape sealing assembly 120 is positioned adjacent second position 132 oftape path assembly 118 and seals an array on tape 104 with seal 106after the biological sample and the reagent are dispensed into tape 104.Thermal management of tape 104 can occur at second position 132. Forexample, tape 104 can be cooled at second position 132 to prevent thebiological sample and reagent mixture from undergoing a chemicalreaction, or tape 104 can be heated at second position 132 to incubatethe biological sample and reagent mixture. Thermal management of tape104 can occur at third position 134 as well. At third position 134, tape104 can again be cooled to prevent the biological sample and reagentmixture from undergoing a chemical reaction or heated to incubate thebiological sample and reagent mixture. Tape 104 waits in third position134 until instrument 100 is prepared to amplify and analyze thebiological sample and reagent mixture in tape 104. At fourth position136, tape 104 can be amplified and analyzed using detection assembly 122that is positioned adjacent fourth position 136 of tape path assembly118. Detection assembly 122 can heat the biological sample and reagentmixture in tape 104 and further includes a camera that can be used toanalyze the biological sample and reagent mixture in tape 104.Electronic assembly 124 is included in instrument 100 to powerinstrument 100 and control the other assemblies in instrument 100.

Instrument 100 is advantageous for a number of reasons. First, each ofthe plurality of assemblies are positioned on a single chassis 102. Thisallows instrument 100 to have a compact design, thus making instrument100 suitable for use in a variety of different settings. Second,instrument 100 is an all-in-one system that is capable of performingeach step necessary to dispense, amplify, and analyze a biologicalsample and reagent mixture that is to be tested in instrument 100. Thisallows instrument 100 to be used without the need for additionalequipment to perform different functions for dispensing, amplifying, andanalyzing the biological sample and reagent mixture. Third, instrument100 can be used for large scale or small scale testing. Instrument 100includes all of the components necessary to test a large number ofbiological samples or a small number of biological samples. Thisversatility allows instrument 100 to be used in a wide range of settingsand for a large number of different applications.

FIG. 2A is an isometric view of instrument 100. FIGS. 2B-2D areperspective views of instrument 100. FIGS. 2E-2F are back perspectiveviews of tape path assembly 118 in instrument 100. Instrument 100includes chassis 102, tape 104, seal 106, plate stacker assembly 110,deck plate assembly 112, dispensing assembly 114, wash assembly 116,tape path assembly 118, tape sealing assembly 120, detection assembly122, and electronic assembly 124. Tape path assembly 118 includes firstposition 130, second position 132, third position 134, and fourthposition 136.

Plate stacker assembly 110 includes plate rack 140, plate stacker 142,and plate shuttle 144. In the embodiment shown in FIGS. 2A-2D, platestacker assembly 110 is used to receive, hold, and move platescontaining a biological sample. In alternate embodiments, plate stackerassembly 110 could also be used to receive, hold, and move platescontaining a reagent. Plate rack 140 is a chute or hotel that canreceive and hold a plurality of plates. Plate rack 140 is attached tochassis 102 of instrument 100 and can be moved in and out of instrument100 using any suitable mechanism, including having a user pull platerack 140 out of instrument 100. Plate stacker 142 includes an arm with aspatula that can move up and down and rotate on a support structure. Thespatula of plate stacker 142 can lift plates out of plate rack 140 andmove them in instrument 100. Plate shuttle 144 includes a nest portionthat can move horizontally along a support structure. Plates from platerack 140 can be moved by plate stacker 142 to the nest portion of plateshuttle 144. When a plate is positioned on the nest portion of plateshuttle 144, the nest portion can move through instrument 100 to bepositioned for aspiration or dispensing.

Plates containing a biological sample and/or a reagent can be placed inplate stacker assembly 110 in two ways. First, plate rack 140 can bepulled out of instrument 100 and plates can be positioned on plate rack140. Second, the nest portion of plate shuttle 144 can extend out ofinstrument 100, as seen in FIGS. 2B and 2D. A plate can then bepositioned on the nest portion of plate shuttle 144 and the nest portioncan then move back into instrument 100. In alternate embodiments, platestacker assembly 110 can further receive a tip tray holder containingtips for dispensing assembly 114, a matrix rack that holds a pluralityof matrix tubes, a well trough, or any other container that is capableof containing a biological sample and/or a reagent.

Deck plate assembly 112 includes deck plate station 150, deck platestation 152, and deck plate station 154. In the embodiment shown inFIGS. 2A-2F, deck plate assembly 112 is used to receive and hold platescontaining a reagent. In alternate embodiments, deck plate assembly 112can be used to receive and hold plates containing a biological sample.Each of deck plate station 150, deck plate station 152, and deck platestation 154 can receive and hold a plate. Deck plate station 150, deckplate station 152, and deck plate station 154 each further include ahold down to hold the plate in place. Plates are positioned on deckplate station 150, deck plate station 152, and deck plate station 154 bylifting up the hold down, positioning the plate, and then lowering thehold down to secure the plate in place. In alternate embodiments, deckplate station 150, deck plate station 152, and deck plate station 154can further receive a matrix rack that holds a plurality of matrixtubes, a well trough, or any other container that is capable ofcontaining a biological sample and/or a reagent.

Dispensing assembly 114 includes sample dispenser 160 and reagentdispenser 162. Sample dispenser 160 and reagent dispenser 162 bothinclude one or more tips that can be used to aspirate and dispensebiological samples and reagents. In alternate embodiments, the tipscould be pin tools that can be used to transfer the biological sampleand/or the reagent. Reagent dispenser 162 is positioned on a side ofsample dispenser 160. Sample dispenser 160 and reagent dispenser 162move together in an x direction and a y direction on a gantry on a topend of instrument 100. In the embodiment shown, when sample dispenser160 moves in a z direction, reagent dispenser 162 will move with sampledispenser 160. Reagent dispenser 162 can further move in a z directionrelative to sample dispenser 160. In the embodiment shown in FIGS.2A-2F, sample dispenser 160 is used to aspirate a biological sample froma plate in plate shuttle 144 and then dispense the biological sampleinto tape 104. Reagent dispenser 162 is used to aspirate a reagent froma plate in deck plate assembly 112 and then dispense the reagent intotape 104. In alternate embodiments, sample dispenser 160 can aspirateand dispense the reagent and reagent dispenser 162 can aspirate anddispense the biological sample.

Wash assembly 116 includes sample dispenser wash 170 and reagentdispenser wash 172. Sample dispenser wash 170 can be used to wash thetips on sample dispenser 160. Sample dispenser wash 170 is a vacuumbased system that can use a cleaning solution and/or water with air flowto evacuate any residual biological sample or reagent from the tips todecontaminate them so they can be reused. An example of sample dispenserwash 170 is disclosed in published PCT application WO 2014/179584, whichis hereby incorporated by reference in its entirety. Reagent dispenserwash 172 is used to wash the tips on reagent dispenser 162. Reagentdispenser wash 172 uses water and air flow to clean the tips.

As shown in FIGS. 2E and 2F, tape path assembly 118 includes firstposition 130, second position 132, third position 134, and fourthposition 136. Tape path assembly 118 also includes tape infeed 180, tapecutter 182, retractable hold down 184, actuating mechanism 186, thermalunit 188, and thermal unit 190. Tape infeed 180 is positioned near afirst end of tape path assembly 118 upstream of first position 130. Tapeinfeed 180 includes a retractable spool that can hold a cartridge oftape 104. Tape infeed 180 is positioned near the first end of tape pathassembly 118 so that tape 104 can be fed into tape path assembly 118.Tape 104 that is fed into tape path assembly 118 can then advance tofirst position 130. Positioned adjacent first position 130 is tapecutter 182. Tape cutter 182 includes a blade that can be actuated upwardto cut tape 104 if desired. Tape 104 can also advance along tape pathassembly 118 without being cut by tape cutter 182.

Tape 104 advances from first position 130 to second position 132 alongtape path assembly 118. In second position 132, the biological sampleand the reagent are dispensed into tape 104 with dispensing assembly 114to form a biological sample and reagent mixture. To hold tape 104 flatduring dispensing, retractable hold down 184 is positioned adjacentsecond position 132 (and on top of third position 134). Retractable holddown 184 includes a retractable bar that can be automatically actuatedto hold tape 104 flat. Positioned beneath second position 132 is thermalunit 188. Thermal unit 188 includes one or more thermoelectric modules(TEMs) that can be used to either cool or heat the biological sample andreagent mixture in tape 104. Positioned adjacent second position 132 istape sealing assembly 120. An array on tape 104 can be sealed with seal106 using tape sealing assembly 120 when that array is positioned insecond position 132.

After dispensing and sealing, tape 104 advances to third position 134.Positioned above third position 134 is retractable hold down 184 to holdtape 104 flat when tape 104 is in second position 132. Positionedbeneath third position 134 is thermal unit 190. Thermal unit 190includes one or more TEMs that can be used to either cool or heat thebiological sample and reagent mixture in tape 104. Tape 104 can wait atthird position 134 until instrument 100 is prepared to amplify andanalyze the biological sample and reagent mixture in tape 104.

When instrument 100 is prepared to amplify and analyze the biologicalsample and reagent mixture, tape 104 can advance to fourth position 136.Positioned beneath fourth position 136 is thermal unit 210 to heat thebiological sample and reagent mixture in tape 104. Positioned abovefourth position 136 is heated pressure chamber 212 to pressurize an areaabove tape 104 to push down on and keep seal 106 on tape 104. Thebiological sample and reagent mixture in tape 104 is amplified usingthermal unit 210 in fourth position 136. Either after or duringamplification, the biological sample and reagent mixture can be analyzedusing camera 214. Heated pressure chamber 212 further heats thebiological sample and reagent mixture and prevents condensation on seal106 on tape 104 to ensure accurate analysis with camera 214.

Tape 104 advances along tape path assembly 118 through instrument 100with actuating mechanism 186. Actuating mechanism 186 is a belt thatdrives tape 104 with frictional engagement in the embodiment shown inFIGS. 2A-2F. In alternate embodiments, actuating mechanism 186 can drivetape 104 with any suitable mechanism. Tape 104 advances throughinstrument 100 along tape path assembly 118 until tape 104 exitsinstrument 100 at a second end of tape path assembly 118.

As shown in FIGS. 2A, 2C, and 2D, tape sealing assembly 120 includesspool 200 and applicator 202. Tape sealing assembly 120 is capable ofmovement in both the x and y directions in relation to instrument 100.Spool 200 can hold a web of seals 106 that can be used to seal tape 104in instrument 100. Seals 106 are cover seals that can be applied to tape104 to contain the biological sample and reagent mixture in tape 104 andprevent evaporation and contamination of the biological sample andreagent mixture in tape 104. Seals 106 that are held on spool 200 arerouted through tape sealing assembly 120 so that applicator 202 cancapture seal 106 as seal 106 is removed from the backing seal 106 isheld on. Applicator 202 can then apply seal 106 to an array of tape 104.Tape sealing assembly 120 is positioned adjacent second position 132 oftape path assembly 118 so that tape 104 can be sealed with seal 106 atsecond position 132.

Detection assembly 122 includes thermal unit 210, heated pressurechamber 212, and camera 214. Detection assembly 122 is positioned atfourth position 136 to amplify and analyze the biological sample andreagent mixture in tape 104. Thermal unit 210 is positioned underneathfourth position 136 and includes one or more TEMs that can be used tohold the biological sample and reagent mixture at a constant temperatureor cycle the biological sample and reagent mixture through multipletemperatures. Heated pressure chamber 212 is positioned above and aroundfourth position 136. Heated pressure chamber 212 seals, pressurizes, andheats the area above fourth position 136 so that the biological sampleand reagent mixture in tape 104 can be analyzed. Heated pressure chamber212 also prevents condensation on seal 106 so that camera 214 canproperly detect a signal from the biological sample and reagent mixturein tape 104.

Detection assembly 122 includes excitation light emitting diodes forilluminating the biological sample and reagent mixture in tape 104 toexcite a dye or probe in the biological sample and reagent mixture. Thedye or probe emits a signal, such as fluorescence, and an emissionfilter wheel filters the signal entering camera 214 to a desiredwavelength. Camera 214 is positioned above fourth position 136 andheated pressure chamber 212 and can detect the signal emitted from thebiological sample and reagent mixture in tape 104. Camera 214 is a CCDcamera in the embodiment shown, but can be any suitable camera or otherdetection device in alternate embodiments.

As shown in FIGS. 2A-2D, electronic assembly 124 includes illuminationstrips 216, power supply 220, printed circuit boards 222, industrial PC224, and display 226. Illumination strips 216 line chassis 102 andprovide additional lighting during operation of instrument 100. In theembodiment shown, illumination strips 216 are light emitting diodes. Inan alternate embodiment, illumination strips 216 can include an ultraviolet light source to aid in decontamination of instrument 100. Powersupply 220 powers instrument 100 and each of the plurality of assembliespositioned in instrument 100. Printed circuit boards 222 includeelectronic components that are used to control the operation ofinstrument 100. Printed circuit boards 222 are positioned in a backportion of instrument 100 and are further located throughout instrument100 to control each of the plurality of assemblies in instrument 100.Industrial PC 224 is also positioned in a back portion of instrument 100and further controls the operation of instrument 100. Industrial PC 224can communicate with printed circuit boards 222 throughout instrument100 to execute the functions of instrument 100. Display 226 ispositioned on a first side of instrument 100 and is a touchscreendisplay that a user can use to control testing in instrument 100.Display 226 can also display data that is collected in instrument 100during operation. Display 226 can be attached to a multidirectional armso that a user can move display 226 to a position suitable for them.Instrument 100 further includes an analytics system to gather andanalyze data that is collected during analysis of the biological sampleand reagent mixture.

Instrument 100 is advantageous over prior art devices, as instrument 100can test a large sample set or a small sample set. This versatilityallows instrument 100 to be used in a variety of settings. Theall-in-one function and compact design further allows instrument 100 tobe used in a variety of different settings and for a wide range ofdifferent applications. Instrument 100 can amplify and analyze abiological sample and reagent mixture according to polymerase chainreaction (PCR) steps. This includes real-time PCR, end-point PCR, andother suitable PCR variations. Real-time PCR (or quantitative PCR)includes thermal cycling and amplifying the biological sample andreagent mixture and detecting a signal from the biological sample andreagent mixture at the same time. End-point PCR includes detecting asignal from the biological sample and reagent mixture after it has beenamplified. The biological sample and reagent mixture can be amplifiedaccording to any suitable process with end-point PCR. Further, thebiological sample and reagent mixture can be dispensed and sealed intape 104 in instrument 100, removed from instrument 100 to undergoamplification using an external device, and then inserted back intoinstrument 100 for end-point detection with instrument 100. Instrument100 can also amplify and analyze a biological sample and reagent mixtureusing isothermal amplification. Isothermal amplification includesamplifying the biological sample and reagent mixture at a constanttemperature. Instrument 100 can also be used for other PCR processes orfor any process that detects a signal from a biological sample andreagent mixture using a camera.

FIG. 3A is a top plan view of thermal management system 240 ininstrument 100. FIG. 3B is a perspective view of thermal managementsystem 240. FIG. 3C is a schematic view of thermal management system240. Instrument 100 includes deck plate assembly 112 (including deckplate station 150, deck plate station 152, and deck plate station 154)and tape path assembly 118 (including second position 132, thirdposition 134, and fourth position 136). Thermal management system 240includes reservoir 242, fluid pump 243, radiator 244, cooling fan 245,fluid path 246, fluid path 248, fluid path 250, fluid path 252, fluidpath 254, fluid path 256, and fluid path 258.

Thermal management system 240 runs through instrument 100 to provide aheat exchange fluid to thermal units that are positioned in instrument100. Thermal management system 240 is a closed-loop fluidic thermalmanagement system. Fluid that is not being used to exchange heat can bestored in reservoir 242. Fluid that is being used to exchange heat canflow through radiator 244 so that the temperature of the fluid can becontrolled. Cooling fan 245 aids in controlling the temperature of thefluid by blowing cooling air across radiator 244 in order to remove heatfrom fluid flowing through radiator 244. Fluid from radiator 244 canthen flow through a plurality of fluid paths in instrument 100.

Fluid path 246 and fluid path 248 are both positioned beneath fourthposition 136 of tape path assembly 118. Fluid path 246 runs on a firstside of fourth position 136 and fluid path 248 runs on a second side offourth position 136. Fluid path 250 is positioned beneath third position134 of tape path assembly 118. Fluid path 252 is positioned beneathsecond position 132 of tape path assembly 118. Fluid path 254 ispositioned beneath deck plate station 154 of deck plate assembly 112.Fluid path 256 is positioned beneath deck plate station 152 of deckplate assembly 112. Fluid path 258 is positioned beneath deck platestation 150 of deck plate assembly 112. Fluid paths 246-258 all includea cavity that curves back and forth through a block so that fluid canflow through the cavity and exchange heat with components that arepositioned above the cavity.

When heat exchange is needed, fluid pump 243 pumps fluid from reservoir242 to radiator 244. Radiator 244 and cooling fan 245 can adjust thetemperature of the fluid for use in instrument 100. After thetemperature of the fluid is regulated, the fluid flows throughinstrument 100 along two separate paths. The first path is through fluidpath 246 and 248, fluid path 250, fluid path 252, and back to reservoir242. The second path is through fluid path 254, fluid path 256, fluidpath 258, and back to reservoir 242. The fluid that flows from radiator244 to fluid paths 246, 248, and 254 is routed through a base portion ofinstrument 100. Further, fluid that flows from fluid paths 252 and 258to reservoir 242 is routed through a base portion of instrument 100.Routing the fluid through a base portion of instrument 100 allows thespace on the main surface of instrument 100 to hold other components.This allows for flexibility in the design of instrument 100 and allowsinstrument 100 to have a compact design.

Thermal management system 240 is advantageous as it is a closed-loopsystem. This means instrument 100 does not have to be connected to afluid source to regulate the temperature of components in instrument100, as the fluid is stored in thermal management system 240 and cycledthrough thermal management system 240 as needed. This allows instrument100 to be used in settings where there is no access to a temperaturecontrolled fluid source. Thermal management system 240 is furtheradvantageous, as it can effectively and efficiently regulate thetemperature of components that are positioned along thermal managementsystem 240 using convective heat transfer.

FIG. 4A is a top plan view of tape 104 with wells 270. FIG. 4B is aschematic view of tape 104 with first plurality of wells 272 and secondplurality of wells 274. Tape 104 includes wells 270, including firstplurality of wells 272 (including well 276), second plurality of wells274 (including well 278), and array identifier 280.

Tape 104 includes wells 270. Wells 270 are formed in tape 104 to receiveand hold a biological sample and a reagent for amplification andanalysis. Tape 104 can include any number of wells 270, including onewell 270 or a plurality of wells 270. For example, tape 104 can includewells 270 arranged in a 96 well configuration, a 192 well configuration,a 384 well configuration, a 768 well configuration, or a 1536 wellconfiguration. Array identifier 280 is an identifier, such as a barcode,which identifies the contents in wells 270. Tape 104 is made out of apolymer material and wells 270 are created by embossing in theembodiment shown, although they can be created using other suitablemethods in alternate embodiments. In the embodiment shown, tape 104 is awhite and opaque tape. In alternate embodiments, tape 104 can be black,white, or gray and transparent, semi-transparent, or opaque.

In the embodiment shown in FIGS. 4A-4B, wells 270 include firstplurality of wells 272 and second plurality of wells 274 that are offsetfrom and interlaced with first plurality of wells 272. As seen in FIG.4B, first plurality of wells 272 are represented with white circles andsecond plurality of wells 274 are represented with black circles. Tape104 includes 768 wells, with 384 wells making up first plurality ofwells 272 and 384 wells making up second plurality of wells 274. Inalternate embodiments, tape 104 can include any number and size of wells270 with a first plurality of wells being interlaced with a secondplurality of wells.

First plurality of wells 272 and second plurality of wells 274 arepositioned on tape 104 so that the wells in first plurality of wells 272and the wells in second plurality of wells 274 are offset from oneanother at a 45-degree angle. For example, well 276 of first pluralityof wells 272 is offset from well 278 of second plurality of wells 274 ata 45-degree angle. Each well in first plurality of wells 272 is offsetfrom each adjacent well in second plurality of wells 274 at a 45-degreeangle. This allows first plurality of wells 272 and second plurality ofwells 274 to be interlaced with one another in an offset pattern.

Interlacing first plurality of wells 272 and second plurality of wells274 with each other on tape 104 is advantageous. If either firstplurality of wells 272 or second plurality of wells 274 were removed, a384-well format would be left on tape 104. Interlacing is advantageousfor a number of reasons. First, tape 104 allows a standard 384-wellformat to be duplicated in essentially the same amount of space aspreviously required for the 384-well format. This doubles the number ofresults that can be collected when a single array of tape 104 is tested,increasing the efficiency and throughput of the testing device. Second,tape 104 can easily interact with standardized equipment, such aspipette tips, that is currently available for the 384-well or 96-wellformat. Third, interlacing first plurality of wells 272 and secondplurality of wells 274 with one another allows for maximum spacingbetween wells 270, allowing for larger wells then would otherwise bepossible. Fourth, the surface area between wells 270 is maximized ontape 104, which is advantageous when tape 104 is sealed. A largersurface area allows for a better seal, as there is more contact betweentape 104 and seal 106.

Plate Stacker Assembly

FIG. 5A is an isometric view of plate stacker assembly 110 in instrument100. FIG. 5B is a top cut away view of plate stacker assembly 110 ininstrument 100. FIG. 5C is an isometric view of plate stacker assembly110. Plate stacker assembly 110 is positioned in a first corner ofinstrument 100. Plate stacker assembly 110 is capable of receiving,holding, and moving plates in instrument 100. In the embodiment shown inFIGS. SA-SC, plate stacker assembly 110 receives plates containing abiological sample. In alternate embodiments, plate stacker assembly 110can receive plates containing other samples or reagents.

Plate stacker assembly 110 includes plate rack 302, plate stacker 304,and plate shuttle 306. Plate rack 302 is a chute or a hotel that canreceive and hold a plurality of plates. Plate rack 302 is attached toinstrument 100 and can be moved in and out of instrument 100 using anysuitable mechanism. Plate stacker 304 includes an arm that can move upand down on and rotate around a support structure with a spatulaattached to the arm. The spatula and the arm of plate stacker 304 canpick plates out of plate rack 302 and move them in instrument 100 withrotational and vertical movement. Plate shuttle 306 includes a nestportion that can move horizontally along a support structure. Platesfrom plate rack 302 can be moved by plate stacker 304 and placed on thenest portion of plate shuttle 306. When a plate is positioned on thenest portion of plate shuttle 306, the nest portion can move throughinstrument 100 to be positioned for aspiration and dispensing.

Plates containing a biological sample can be placed in plate stackerassembly 110 in two ways. First, plate rack 302 can be pulled out ofinstrument 100 and plates containing a biological sample can bepositioned on plate rack 302. Second, the nest portion of plate shuttle306 can extend out of instrument 100 (as seen in FIG. 8B). This allowsinstrument 100 to interface with plate storage units or plate lidremoval equipment outside of instrument 100. A plate can then bepositioned on the nest portion of plate shuttle 306 and the nest portioncan then move back into instrument 100.

Plate stacker assembly 110 can receive, hold, and move plates or othercomponents compatible with instrument 100, such as tip trays fordispensing assembly 114. Further, plate stacker assembly 110 cancomplete these functions in a small area. This makes plate stackerassembly 110 advantageous for use in instrument 100, which is a compactinstrument with limited space.

FIG. 6A is an isometric view of plate rack 302. FIG. 6B is a top planview of nest 312 of plate rack 302. Plate rack 302 includes frame 310,nests 312, rails 314, rails 315, handles 316, and contact 318, as shownin FIG. 6A. Each nest 312 includes frame 320, corner supports 322,opening 324, and slot 326, as shown in FIG. 6B.

Plate rack 302 includes frame 310 that forms a body portion of platerack 302. As seen in the embodiment shown in FIGS. 6A-6B, attached toframe 310 are a plurality of nests 312. In alternate embodiments, onenest 312 or any number of nests 312 can attached to frame 310. Nests 312are positioned in a vertical row on frame 310. Each nest 312 can receiveand hold a plate. When a plate is needed for aspiration or dispensing,the plate can be picked from nest 312 that the plate is positioned inand moved through instrument 100 to be positioned for aspiration ordispensing.

Rails 314 are attached to frame 310 on an outer side surface of frame310. Rails 314 are sliding rails in the embodiment shown in FIG. 6A thatslide upon corresponding rails 315 that can be attached to instrument100. Rails 314 and rails 315 allow plate rack 302 to slide in and out ofinstrument 100. In alternate embodiments, rails 314 and rails 315 can beany mechanism that holds plate rack 302 in instrument 100 and allowsplate rack 302 to slide in and out of instrument 100. In someembodiments, when plate rack 302 is slid out of instrument 100 platerack 302 can be fully removed. This allows a user to remove plate rack302, load plate rack 302 with plates at a location away from instrument100, and then reinsert plate rack 302 into instrument 100 once plateshave been positioned on plate rack 302. Handles 316 are attached to anouter front surface of frame 310. Handles 316 can be grasped by a userto slide plate rack 302 out of instrument 100 along rails 314 and rails315. Handles 316 can also be used to move plate rack 302 when plate rack302 is removed from instrument 100.

Contact 318 is also attached to an outer side surface of frame 310.Contact 318 will abut a contact that is attached to instrument 100 whenplate rack 302 is positioned in instrument 100. Contact 318 and thecontact attached to instrument 100 act as a sensor to indicate toinstrument 100 that plate rack 302 is positioned in instrument 100.Further, contact 318 can communicate to the contact attached toinstrument 100 to indicate what configuration or size of plate rack 302has been placed in instrument 100. In alternate embodiments, anyidentification mechanism can be positioned on plate rack 302 and anyidentification reader can be positioned on instrument 100. As a firstexample, a barcode affixed to frame 310 of plate rack 302 could bescanned by a camera on instrument 100 and used to indicate whatconfiguration or size of plate rack 302 has been placed in instrument100. As a second example, an RFID tag affixed to frame 310 of plate rack302 could be scanned by an RFID reader on instrument 100 and used toindicate what configuration or size of plate rack 302 has been placed ininstrument 100. This information can then be used by instrument 100 toindicate to components that interact with plate rack 302 whatconfiguration and size of plate rack 302 is in instrument 100.

As seen in FIG. 6B, each nest 312 includes frame 320 that forms an outerbody portion of nest 312. Frame 320 has a beveled inner edge to guide aplate being placed on nest 312 into the proper position. The beveledinner edge on frame 320 eliminates the need for a plate to be perfectlyaligned with nest 312 before it is placed. Attached to each inner cornerof frame 320 is a corner support 322. Corner supports 322 are flatsupport structures that are each capable of supporting a corner of aplate when a plate is positioned in nest 312. Positioned inwards offrame 320 and corner supports 322 is opening 324. Positioned on a sideof frame 320 is slot 326. Opening 324 and slot 326 are provided in eachnest 312 so that an arm can pass through nest 312 to place plates innest 312 and to pick plates from nest 312. Slot 326 is positioned on theside of frame 320 through which the arm will pass. Allowing an arm topass through opening 324 and slot 326 allows plate rack 302 to have acompact design.

FIG. 7A is an isometric view of plate stacker 304. FIG. 7B is aperspective view of a portion of plate stacker 304 and a portion ofplate rack 302. 7C is a perspective view of a portion of plate stacker304. Plate stacker 304 includes column 330, screw rail 332, arm 334,spatula 336, actuator 338, actuator 340, camera 342, bracket 343, cablecarrier 344, sensor 346, mirror 348, and mirror 349. Spatula 336includes support member 350 and notches 352. Also shown in FIG. 7B isplate 390A positioned on plate rack 302. Also shown in FIGS. 7B and 7Cis camera path C.

Plate stacker 304 includes column 330 that forms a support structure forplate stacker 304. Positioned inside column 330 is screw rail 332. Arm334 is attached to screw rail 332. Arm 334 includes spatula 336 that canbe used to pick and place plates in instrument 100. Arm 334 can move upand down in a vertical direction on screw rail 332. Arm 334 can alsorotate with column 330 about a vertical axis. Actuator 338 is positionedon a base portion of plate stacker 304 and controls the rotationalmovement of column 330 and arm 334. Actuator 340 is positioned on a topend of column 330 and controls the vertical movement of arm 334 on screwrail 332. In the embodiment shown, actuator 340 includes a servo motorthat tracks the vertical position of arm 334 on screw rail 332.

Camera 342 is attached to plate stacker 304 with bracket 343. Camera 342is used to scan barcodes or other plate identifiers on plates that arepositioned in instrument 100. In the embodiment shown in FIG. 7B, camera342 is used to scan barcodes on plates positioned in plate rack 302.Camera 342 is attached to bracket 343 so that camera 342 moves up anddown with arm 334 on screw rail 332. Camera path C shows the path from abarcode on plate 390A to camera 342. Camera 342 is positioned such thatcamera 342 captures the image of the barcode reflected in mirrors 348and 349. Scanning barcodes with camera 342 allows instrument 100 todetermine what plate should be moved with spatula 336. Cable carrier 344is positioned adjacent column 330 and contains cables that connectcamera 342 to a power source and other electronic components that areneeded to communicate with instrument 100. Also attached to platestacker 304 is sensor 346. Sensor 346 senses the presence of a plate onspatula 336.

Spatula 336 of arm 334 is used to pick and place plates in instrument100. Spatula 336 includes support member 350 and notches 352. Supportmember 350 is a base portion with a plus shape. Notches 352 are openareas in each corner of spatula 336. Support member 350 and notches 352are shaped so that spatula 336 can pass through nests in instrument 100.Support member 350 is used to engage a bottom of a plate in instrument100. This engagement supports a plate and allows spatula 336 to move theplate in instrument 100. Support member 350 has a beveled inner edge toguide a plate being picked with spatula 336 into the proper position.The beveled inner edge on support member 350 eliminates the need for aplate to be perfectly aligned with spatula 336 before it is picked.Using spatula 336 to move plates in instrument 100 is advantageous, assupport member 350 of spatula 336 fully supports a plate and eliminatesconcerns that the plate will be dropped as it is moved in instrument100.

FIG. 8A is an isometric view of plate shuttle 306. FIG. 8B is anisometric view of plate shuttle 306 in instrument 100. Plate shuttle 306includes support 360, rail 362, nest 364, bracket 366, driving mechanism368 (including drive belt 369 and actuator 370), clamp 372, home sensor374, and plate sensor 378. Nest 364 includes frame 380, corner supports382, opening 384, and slot 386.

Plate shuttle 306 includes support 360 that forms a support structurefor plate shuttle 306. Support 360 extends in a horizontal directionthrough instrument 100. Attached to support 360 is rail 362. Rail 362also extends in a horizontal direction through instrument 100 alongsupport 360. Nest 364 can be attached to rail 362 with bracket 366. Nest364 moves along rail 362 in a horizontal direction through instrument100. Bracket 366 attaches nest 364 to rail 362. Bracket 366 attachesnest 364 to driving mechanism 368 with clamp 372. Driving mechanism 368is a belt driven system in the embodiment shown in FIGS. 8A-8B, but canbe any suitable driving mechanism in alternate embodiments. Actuator 370is attached to support 360 and controls the movement of drivingmechanism 368. Bracket 366 attaches to drive belt 369 of drivingmechanism 368 with clamp 372. As drive belt 369 of driving mechanism 368moves, clamp 372 will move with drive belt 369 and thus will movebracket 366. As bracket 366 moves with driving mechanism 368, bracket366 will slide upon rail 362 and move nest 364 in instrument 100.

Also attached to support 360 are home sensor 374, and plate sensor 378.Home sensor 374 is positioned on a first end of support 360. Home sensor374 senses when nest 364 is positioned near the first end of support360. This is the home position for nest 364. As seen in FIG. 8B, nest364 can extend out of instrument 100 through an opening in instrument100. Plate sensor 378 is positioned between the middle portion and thefirst end of support 360. Plate sensor 378 senses when a plate ispositioned on nest 364. When a plate is positioned on nest 364, platesensor 378 will indicate to instrument 100 that there is a platepositioned on nest 364 to prevent instrument 100 from trying to placeanother plate on nest 364. When a plate is positioned on nest 364, platesensor 378 will also indicate to instrument 100 that a plate isavailable for dispensing operations.

As seen in FIG. 8A, nest 364 includes frame 380 that forms an outer bodyportion of nest 364. Frame 380 has a beveled inner edge to guide a platebeing placed on nest 364 into the proper position. The beveled inneredge on frame 380 eliminates the need for a plate to be perfectlyaligned with nest 364 before the plate is placed. Attached to each innercorner of frame 380 is a corner support 382. Corner supports 382 areflat support structures that are each capable of supporting a corner ofa plate when a plate is positioned in nest 364. Positioned inward offrame 380 and corner supports 382 is opening 384. Positioned on a sideof frame 380 is slot 386. Opening 384 and slot 386 are provided in nest364 so that arm 334 of plate stacker 304 can pass through nest 364 toplace plates in nest 364 and to pick plates from nest 364. Slot 326 ispositioned on the side of frame 320 through which arm 334 will pass.Allowing arm 334 to pass through opening 384 and slot 386 of nest 364allows a plate to be easily picked from or placed into nest 364.

FIG. 9A is an isometric view of plate rack 302 and plate stacker 304when spatula 336 is in a home position. FIG. 9B is an isometric view ofplate rack 302 and plate stacker 304 when spatula 336 has been movedfrom the home position. FIG. 9C is an isometric view of plate rack 302and plate stacker 304 when spatula 336 is positioned to pick plate 390A.FIG. 9D is a perspective view of plate stacker 304 and plate shuttle 306when spatula 336 has placed plate 390A in nest 364 of plate shuttle 306.Plate rack 302 includes frame 310, plurality of nests 312 (includingnest 312A), and rails 314. Each nest 312 includes frame 320, cornersupports 322, opening 324, and slot 326 (as shown in FIG. 6B). Platestacker 304 includes column 330, screw rail 332, arm 334, spatula 336,actuator 338, actuator 340, camera 342, cable carrier 344, and sensor346. Spatula 336 includes support member 350 and notches 352. Plateshuttle 306 includes support 360, rail 362, nest 364, bracket 366,driving mechanism 368, home sensor 374, and plate sensor 378. Nest 364includes frame 380. Also shown are plates 390 (including plate 390A).

As seen in FIG. 9A, plate stacker 304 is in a home position when arm 334with spatula 336 is positioned over a top end of plate rack 302. To movearm 334 out of the home position, actuator 338 will rotate arm 334 andcolumn 330 so that arm 334 is no longer positioned over plate rack 302.Actuator 340 can then move arm 334 up and down along screw rail 332.

As seen in FIG. 9B, arm 334 has been rotated and vertically moved awayfrom the home position. This prepares plate stacker 304 to pick a plateout of plate rack 302. To pick a plate out of plate rack 302, actuator340 moves arm 334 vertically so that arm 334 is aligned just below abottom surface of nest 312 containing the plate that is to be picked.Actuator 338 then rotates arm 334 until spatula 336 is positionedunderneath the plate that is to be picked. Spaces are left between eachnest 312 in plate rack 302 to allow spatula 336 to move between nests312.

As seen in FIG. 9C, spatula 336 is positioned underneath plate 390A innest 312A at the bottom end of plate rack 302. After spatula 336 isrotated to this position, actuator 340 can move arm 334 upward so thatspatula 336 engages and picks plate 390A positioned on nest 312A.Actuator 340 drives screw rail 332 to move arm 334 and spatula 336upward to pick plate 390A so that plate 390A no longer touches nest 312Aand so that plate 390A and spatula 336 are positioned just above a topsurface of nest 312A. This allows actuator 338 to rotate arm 334 awayfrom plate rack 302, thus moving plate 390A out of plate rack 302.

When spatula 336 engages plate 390A in nest 312A of plate rack 302,spatula 336 and arm 334 pass through opening 324 and slot 326 of nest312A. Support member 350 engages a bottom side of plate 390A and picksplate 390A off of corner supports 322 of nest 312A. Notches 352 ofspatula 336 are sized and shaped so that they pass next to cornersupports 322. This allows spatula 336 to move through opening 324.

After plate 390A has been picked out of plate rack 302, arm 334 andspatula 336 are rotated away from plate rack 302 and positioned aboveplate shuttle 306. Plate shuttle 306 then moves nest 364 into a positionto receive plate 390A from plate stacker 304. Arm 334 and spatula 336are then lowered. As arm 334 and spatula 336 are lowered, spatula 336passes through opening 384 and slot 386 of nest 364. Notches 352 ofspatula 336 pass around corner supports 382 of nest 364. As spatula 336passes through nest 364, each corner of plate 390A on spatula 336 willcome into contact with one corner support 382. This will pick plate 390Aoff of spatula 336 as spatula 336 passes through nest 364, as seen inFIG. 9D. Plate shuttle 306 can then move nest 364 into position foraspiration or dispensing and instrument 100 can aspirate or dispense afluid from plate 390A on nest 364.

After aspiration, plate 390A can be picked from nest 364 with arm 334 ofplate stacker 304. To pick plate 390A from nest 364, spatula 336 and arm334 of plate stacker 304 first need to be positioned below the positionwhere plate 390A will be picked. Plate shuttle 306 can then move nest364 so that nest 364 is positioned over spatula 336 and arm 334. Spatula336 and arm 334 can then be driven upward by actuator 340. Spatula 336and arm 334 will pass through nest 364 and engage and pick plate 390Athat was positioned on nest 364. When spatula 336 engages plate 390A innest 364 of plate shuttle 306, spatula 336 and arm 334 pass throughopening 384 and slot 386 of nest 364 (shown in FIG. 8A). Support member350 engages a bottom side of plate 390A and picks plate 390A off ofcorner supports 382 of nest 364. Notches 352 of spatula 336 are sizedand shaped so that they pass next to corner supports 382. This allowsspatula 336 to move through opening 384.

After plate 390A has been picked out of nest 364 of plate shuttle 306,arm 334 and spatula 336 can be moved vertically until they are alignedjust above a top surface one nest 312 in plate rack 302 in which plate390A is to be placed. If nest 312 in which plate 390A is to be placed islower than nest 364 of plate shuttle 306, plate shuttle 306 will need tomove nest 364 out of the way before arm 334 and spatula 336 can be movedvertically into a position just above a top surface of one nest 312 inplate rack 302. Once arm 334 and spatula 336 are aligned just above onenest 312 in plate rack 302, actuator 338 can rotate arm 334 and spatula336. This will position arm 334 and spatula 336 just over a top surfaceof nest 312 in which plate 390A is to be placed. Actuator 340 can thenlower arm 334 and spatula 336. This will cause arm 334 and spatula 336to pass through opening 324 and slot 326 of nest 312. As spatula 336passes through nest 312, each corner of plate 390A on spatula 336 willcome into contact with one corner support 322. This will pick plate 390Aoff of spatula 336 as spatula 336 passes through nest 312. Spatula 336will then be positioned just below a bottom surface of nest 312 andactuator 338 can rotate spatula 336 and arm 334 out of plate rack 302.

Plate rack 302 can hold any number of plates 390. When one plate 390 isneeded, plate stacker 304 can use camera 342 to determine which plate390 arm 334 should engage. This allows a user to place plates 390 onnests 312 of plate rack 302 in any order. This is advantageous, as itallows for great flexibility in using instrument 100. A user does notneed to determine the order of testing before setting up instrument 100,as instrument 100 will be able to select and move plates 390 in anyorder.

Plate stacker assembly 110 is further advantageous, as arm 334 andspatula 336 provide firm contact and engagement with plates ininstrument 100. Prior art systems grip plates with a robotic arm to movethem in instrument 100. Picking plates 390 with spatula 336 providesbetter contact with plates 390, ensuring that plates 390 will movethrough instrument 100 without being dropped. This makes plate stackerassembly 110 more reliable than prior art systems.

Plate stacker assembly 110 is also advantageous, as it allows forrotational movement and vertical movement about a common z-axis. Thismovement around a common z-axis allows plate stacker assembly 110 tohave a compact design. This saves space in instrument 100 while stillallowing for a large range of motion for moving plates in instrument100.

Deck Plate Assembly

FIG. 10 is an isometric view of deck plate assembly 112 withininstrument 100. Deck plate assembly 112 includes deck plate station 402,deck plate station 404, and deck plate station 406. Deck plate station402, deck plate station 404, and deck plate station 406 hold plates orracks containing reagents (reagent plates). Dispensing assembly 114 ofinstrument 100 dispenses the reagents into tape 104 proceeding throughinstrument 100. In alternate embodiments, deck plate station 402, deckplate station 404, and deck plate station 406 can be used to receive andhold plates or racks containing biological samples. In alternateembodiments, deck plate assembly 112 can include a single deck platestation, two deck plate stations, or four or more deck plate stations.

FIG. 11A is a partially transparent isometric view of deck plate station406. FIGS. 11B-11D are perspective views of deck plate station 406. Asshown in FIGS. 11A-11D, deck plate station 406 includes housing 408,deck cover 410 (shown transparent in FIG. 11A) with A1 position 412,thermoelectric modules (TEMs) 414, temperature sensor 416, spring-loadedclip 418, hold down 420 with clover leaf pattern 422, pivot 424, lockknob 426, drain port 428, fluid inlet port 430, fluid outlet port 432,hold down height adjustment screw 434, mirror 474, and camera 476. Inthe embodiment shown in FIGS. 11B and 11D, plate 442 with wells 444rests on deck cover 410. In an alternative embodiment shown in FIG. 11C,rack 446 with plurality of matrix tubes 448 rests on deck cover 410.Plurality of matrix tubes 448 includes resealable caps. In alternativeembodiments, any suitable plate or rack can rest on deck cover 410.Camera 476 captures an image of a barcode on plate 442 or rack 446 usingmirror 474 (see FIG. 16 for more detail).

Housing 408 surrounds deck cover 410. TEMs 414 and temperature sensor416 are located underneath deck cover 410. TEMs 414 provide thermalmanagement of deck cover 410. For example, when plate 442 is placed ondeck cover 410, deck cover 410 can cool plate 442 to a desiredtemperature. Plate 442 can be a plate containing reagents in wells 444,and deck cover 410 can cool plate 442 in order to prevent the reagentsin wells 444 from denaturing, degrading, or otherwise reacting.Temperature sensor 416 provides feedback in order to maintain deck cover410 at a desired temperature. Fluid inlet port 430 and fluid outlet port432 are connected to thermal management system 240 of instrument 100 toprovide a heat sink for TEMs 414 (see FIGS. 13-14 for more detail).

Plate 442 is secured and aligned in A1 position 412 on deck cover 410with spring-loaded clip 418. Spring-loaded clip 418 is attached to deckcover 410 and can be retracted in order to place plate 442 onto deckcover 410. Spring-loaded clip 418 includes a spring that allowsspring-loaded clip 418 to secure plate 442 on deck cover 410. When plate442 is placed onto deck cover 410, spring-loaded clip 418 secures plate442 such that the first well of wells 444 is aligned in A1 position 412.Aligning plate 442 in A1 position 412 aligns wells 444 of plate 442 suchthat the holes of clover leaf pattern 422 align with wells 444 of plate442 such that dispensing assembly 114 of instrument 100 can accuratelylocate wells 444 and aspirate the contents of wells 444 from plate 442.

Drain 428 is located on housing 408. When plate 442 is cooled on deckcover 410, condensation may accumulate on plate 442 and on deck cover410. Housing 408 is shaped with an angled trough such that condensationis directed away from plate 442 and deck cover 410 and exits deck platestation 406 through drain 428.

Hold down 420 is in the open position in FIGS. 11B and 11C and in theclosed position in FIG. 11D. When hold down 420 is in the open position,plate 442 or rack 446 may be placed onto deck plate station 406. Whenhold down 420 is in the closed position, plate 442 or rack 446 issecured on deck cover 410 and the contents of wells 444 or plurality ofmatrix tubes 448 may be aspirated from plate 442. Plate 442 can includea seal over each well 444. Dispensing assembly 114 of instrument 100uses tips to break the seal over each well 444 and aspirate a reagentfrom each well 444. Hold down 420 secures plate 442 on deck cover 410such that plate 442 is not lifted off of deck plate station 406 when thetips are retracted after having punctured through the seal over eachwell 444.

Pivot 424 is connected to hold down 420 and allows a user to manuallypivot hold down 420 between the open position and the closed position.Lock knob 426 is connected to pivot 424 and allows a user to manuallysecure hold down 420 in the open position or the closed position. In theembodiment shown, lock knob 426 is a spring-loaded retractable plunger.In order to lock or unlock hold down 420 and move hold down 420 to theopen or closed position, the user pulls lock knob 426 away from pivot424, turns lock knob 426 half a rotation, pivots hold down 420 up ordown to the open or closed position, turns lock knob 426 a halfrotation, and releases lock knob 426.

Hold down 420 includes clover leaf pattern 422 in order to accommodatevariations in wells 444 of plate 442 and plurality of matrix tubes 448of rack 446. Clover leaf pattern 422 includes 96 four-leaf clover-shapedholes. In the embodiment shown in FIG. 11D, plate 442 includes 96 wells.When hold down 420 is in the closed position, as shown in FIG. 11D, thecenter of each four-leaf clover-shaped hole of clover leaf pattern 422is aligned with one of wells 444 such that each well 444 is accessiblefor dispensing. In an alternative embodiment, plate 442 may include 384wells. In this alternative embodiment, when hold down 420 is in theclosed position, each leaf of each four-leaf clover-shaped hole ofclover leaf pattern 422 is aligned with one of wells 444 such that eachwell 444 is accessible for dispensing.

FIGS. 12A and 12B are partially transparent perspective views of deckplate station 406. Deck plate station 406 includes housing 408, deckcover 410, spring-loaded clip 418, hold down 420 with clover leafpattern 422, pivot 424, lock knob 426, fluid outlet port 432, hold downheight adjustment screw 434, rail clamp nut 436, guides 460, and rail464 (shown partially transparent in FIGS. 12A and 12B).

Hold down height adjustment screw 434 is connected to rail clamp nut436. Rail clamp nut 436 is installed into a groove of rail 464 so thatrail clamp nut can slide freely. Rail clamp nut 436 and hold down heightadjustment screw 434 cooperate to clamp rail 464 against one of guides460 to keep hold down 420 at a desired height. Hold down heightadjustment screw 434 allows the user to manually adjust the height ofhold down 420 up and down in order to accommodate different heights ofplate 442 or rack 446 and to vary how tightly hold down 420 is securedto plate 442 or rack 446.

When a user loosens hold down height adjustment screw 434 (using, forexample, a hex key), rail clamp nut 436 releases rail 464 such that theuser can manually adjust the height of hold down 420 up or down. Rail464 slides up and down within guides 460. Once the desired height isselected based on the height of plate 442 or rack 446, the user tightenshold down adjustment screw 434 to secure the position of hold down 420.As hold down adjustment screw 434 is tightened, rail clamp nut 436 pullsrail 464 over to one of guides 460 to secure hold down 420 at thedesired height. Hold down 420 is held in place on plate 442 or rack 446with friction and gravity.

FIG. 13 is a partially transparent isometric view from underneath deckplate station 406. Deck plate station 406 includes housing 408, deckcover 410, hold down 420 with clover leaf pattern 422, lock knob 426,fluid inlet port 430, fluid outlet port 432, guides 460, and jacket 466with fluid path 468.

Jacket 466 with fluid path 468 is located underneath deck cover 410(shown in FIGS. 11A-11D). TEMs 414 are located between jacket 466 anddeck cover 410. Housing 408 surrounds jacket 466. Fluid path 468 isconnected to thermal management system 240 of instrument 100 throughfluid inlet port 430 and fluid outlet port 432.

FIG. 14 is a bottom view of deck plate station 406. Deck plate stationincludes housing 408, TEMs 414 (shown in phantom), fluid inlet port 430,fluid outlet port 432, and jacket 466 with fluid path 468. As shown inFIGS. 13 and 14, fluid flows through fluid path 468 in order to providethermal management, such as cooling, and can create a heat sink for theheat generated by TEMs 414.

Fluid path 468 is a cavity that snakes back forth within jacket 466.Fluid, such as cooling water, enters fluid path 468 through fluid inletport 430, passes through fluid path 468, and exits fluid path 468through fluid outlet port 432. Jacket 466 with fluid path 468 provides aheat sink that removes heat generated by TEMs 414 when TEMs 414 areoperating to cool deck cover 410. Housing 408 is made of a phenolicmaterial to provide insulation such that the heat from TEMs 414 does notreach deck cover 410. In alternate embodiments, housing 408 can be madeof any other insulating material.

FIG. 15 is a partially transparent side view of deck plate station 406.Deck plate station 406 includes housing 408, drain port 428, hold down420, pivot 424, and limit switch 470. Limit switch 470 detects theposition of hold down 420, including whether hold down 420 is in theopen position or in the closed position (FIGS. 11B and 11D). Limitswitch 470 provides a signal to instrument 100 to prevent otherassemblies such as dispensing assembly 114 from running into deck platestation 406.

FIG. 16 is a side view of deck plate station 406 of deck plate assembly112 within instrument 100. Deck plate station 406 is representative ofdeck plate station 402 and deck plate station 404. Deck plate station406 includes housing 408, hold down 420, plate 442 with barcode 472,mirror 474, and camera 476. Also shown in FIG. 16 is camera path P.

Barcode 472 is located on plate 442. Barcode 472 identifies the contentsof plate 442. Plate 442 is positioned in deck plate assembly 406 suchthat barcode 472 is reflected in mirror 474. Camera path P shows thepath from barcode 472 to camera 476. Camera 476 is positioned such thatcamera 476 captures the image of barcode 472 reflected in mirror 474.Camera 476 captures the image of barcode 472, which allows instrument100 to identify the contents of plate 442.

Tape Path Assembly

FIG. 17A is an isometric view of tape path assembly 118 in instrument100. FIG. 17B is a front isometric view of tape path assembly 118. Tapepath assembly 118 includes first position 130, second position 132,third position 134, fourth position 136, tape infeed 510, tape spool512, drive mechanism 514, tape cutter 516, lift mechanism 518,retractable hold down 520, and covers 522. Covers 522 include tapereceiving ends 524. Tape path assembly 118 also includes entrance ENT ata first end and exit EXT at a second end. Also shown in FIG. 17B is tape104.

Tape path assembly 118 extends through instrument 100 and provides apath along which tape 104 having a plurality of wells can advance. Tape104 moves through instrument 100 from entrance ENT to exit EXT of tapepath assembly 118 through the different positions on tape path assembly118. First position 130 is positioned between entrance ENT and secondposition 132; second position 132 is positioned between first position130 and third position 134; third position 134 is positioned betweensecond position 132 and fourth position 136; and fourth position 136 ispositioned between third position 134 and exit EXT. Different functionsare completed at each position along tape path assembly 118.

Tape infeed 510 is positioned adjacent entrance ENT and can be extendedto a loading position (not shown in FIGS. 17A-17B) for loading tapespool 512. Tape infeed 510 can then be retracted to retracted positionR, where tape infeed 510 and tape spool 512 can be enclosed withininstrument 100. At retracted position R, tape 104 can be driven towardentrance ENT and advanced along tape path 118 toward exit EXT. In thismanner, tape infeed 510 allows for manual loading of tape spool 512,while tape 104 can be automatically advanced within instrument 100,reducing the likelihood of contamination of the wells. Tape infeed 510also allows for the continuous infeed of a desired length of tape 104for processing and analysis. Specifically, tape 104 is guided betweenentrance ENT and exit EXT, tape 104 can be cut to a desired length,processed, and analyzed along a single, compact pathway.

After tape 104 has been fed into tape path assembly 118 with tape infeed510, tape 104 can advance to first position 130. Tape 104 automaticallyadvances along tape path assembly 118 using drive mechanism 514. Drivemechanism 514 is positioned under a top surface of tape path assembly118 and includes a belt that can be used to drive tape 104 along tapepath assembly 118. At first position 130, tape 104 can be cut with tapecutter 516 so any number of arrays of wells can advance throughinstrument 100, including a tape segment with a single array of wells.Alternatively, tape 104 can advance as a web through first position 130without being cut. At second position 132, dispensing assembly 114 (notshown in FIGS. 17A-17B) can dispense a biological sample and a reagentinto tape 104 to form a biological sample and reagent mixture. Further,tape sealing assembly 120 (not shown in FIGS. 17A-17B) can be positionedadjacent to second position 132 to seal the biological sample andreagent mixture in tape 104. Positioned below second position 132 andfourth position 136 is lift mechanism 518. Lift mechanism 518 raisessecond position 132 and fourth position 136 when tape 104 is held in astationary position on tape path assembly 118, but can lower secondposition 132 and fourth position 136 when tape 104 is being advancedalong tape path assembly 118. Positioned adjacent to second position 132and over third position 134 is retractable hold down 520. Retractablehold down 520 can extend toward second position 132 to hold tape 104flat while in second position 132 during dispensing.

Tape 104 can also be cooled at second position 132 to prevent thebiological sample and reagent mixture from undergoing a chemicalreaction, or tape 104 can be heated at second position 132 to incubatethe biological sample and reagent mixture. At third position 134, tape104 can again be cooled to prevent the biological sample and reagentmixture from undergoing a chemical reaction or heated to incubate thebiological sample and reagent mixture. At third position 134, tape 104can be held in place while tape 104 downstream from third position 134is processed at fourth position 136. At fourth position 136, thebiological sample and reagent mixture in tape 104 can be amplified andanalyzed using detection assembly 122 (not shown in FIGS. 17A-17B) thatis positioned adjacent to fourth position 136. The biological sample andreagent mixture can undergo thermal cycling or be heated at a constanttemperature at fourth position 136 with detection assembly 122.Detection assembly 122 further includes a camera (not shown in FIGS.17A-17B) that can be used to analyze the biological sample and reagentmixture in tape 104. In this manner, tape path assembly 118 has acompact design, making the instrument suitable for use in a variety ofdifferent settings.

Covers 522 are located above first position 130, above third position134, and between fourth position 136 and exit EXT. Covers 522 can spanthe width of tape 104 and include tape-receiving ends 524 at a first endof each cover 522. Covers 522 can be v-shaped at tape-receiving ends524. In the embodiment shown in FIGS. 17A-17B, covers 522 are made fromstainless steel. In alternate embodiments, covers 522 can be made fromany suitable material. Covers 522 can prevent tape 104 from bendingupward off of tape path assembly 118.

FIG. 18A is a front isometric view of tape path assembly 118 with tapeinfeed 510 in a retracted position R. FIG. 18B is a front isometric viewof tape path assembly 118 seen in FIG. 18A with tape infeed 510 in anextended position E. Tape path assembly 118 includes first position 130,second position 132, third position 134, fourth position 136, tapeinfeed 510, and tape spool 512. Tape path assembly 118 also includesentrance ENT at a first end and exit EXT at a second end. Also shown inFIGS. 18A-18B is tape 104.

Tape infeed 510 is adjacent to entrance ENT. When tape infeed 510 is atretracted position R (as shown in FIG. 18A), tape 104 is advanced fromtape spool 512 through tape infeed 510 toward first position 130 by aplurality of rollers (not shown in detail in FIGS. 18A-18B). When tapeinfeed 510 is at extended position E (as shown in FIG. 18B), tape spool512 holding tape 104 can be loaded into tape infeed 510. In this manner,tape 104 can be manually loaded into instrument 100 but automaticallyadvanced along tape path assembly 118 by tape infeed 510.

FIG. 19A is a back perspective view of tape path assembly 118 with drivemechanism 514. FIG. 19B is a back isometric view of drive mechanism 514.FIG. 19C is a perspective view of one of rollers 550 of tape pathassembly 118. Tape path assembly 118 includes first position 130, secondposition 132, third position 134, fourth position 136, drive mechanism514, and covers 522. Drive mechanism 514 includes shaft 532, idlerpulleys 536, drive belts 538, actuator 540, actuator drive pulleys 542,idler guide pulleys 544, rollers 550, and springs 552. Tape pathassembly 118 also includes entrance ENT at a first end and exit EXT at asecond end. Also shown in FIG. 19A is tape 104.

Tape 104 advances along tape path assembly 118 through instrument 100via drive mechanism 514. Drive mechanism 514 includes idler pulleys 536positioned near entrance ENT of tape path assembly 118. Idler pulleys536 are mounted on each side of tape path assembly 118. Drive mechanism514 also includes actuator drive pulleys 542 and idler guide pulleys 544positioned near exit EXT of tape path assembly 118. Actuator drivepulleys 542 and idler guide pulleys 544 are mounted on each side of tapepath assembly 118. Actuator drive pulleys 542 are connected to oneanother with shaft 532. Drive belts 538 extend between and wrap aroundactuator drive pulleys 542 and idler pulleys 536. Idler guide pulleys544 keep drive belts 538 aligned with actuator drive pulleys 542 andidler pulleys 536. In the embodiment shown, there are two idler pulleys536, two actuator drive pulleys 542, four idler guide pulleys 544, andtwo drive belts 538. One idler pulley 536, one actuator drive pulley542, two idler guide pulleys 544, and one drive belt 538 are positionedon each of a front side and a back side of tape path assembly 118 andare positioned in parallel at approximately a width of tape 104. On eachside, actuator drive pulley 542 is aligned with idler pulley 536 so thatdrive belt 538 can wrap around each of actuator drive pulley 542 andidler pulley 536.

Drive belts 538 are driven by actuator 540. Actuator 540 is attached toshaft 532. Shaft 532 extends between actuator drive pulleys 542. In theembodiment shown in FIGS. 19A-19C, actuator 540 is a motor. In alternateembodiments, actuator 540 can actuate drive belts 538 with any suitablemechanism such as, for example, an electric motor, a pneumatic motor, ora hydraulic motor. Actuator 540 rotates shaft 532 and actuator drivepulleys 542, which transfer movement to drive belts 538. Drive belts 538move around idler pulleys 536, drive pulleys 542, and idler guidepulleys 544. Idler guide pulleys 544 keep drive belts 538 aligned withactuator drive pulleys 542 and idler pulleys 536.

Rollers 550 are located along both sides of tape path assembly 118between entrance ENT and exit EXT. Rollers 550 are located directlyabove drive belts 538. As seen in FIG. 19C, rollers 550 arespring-loaded with springs 552. Springs 552 hold rollers 550 incompression against drive belts 538. Tape 104 is positioned betweenrollers 550 and drive belts 538. As drive belts 538 are driven, tape 104will move with drive belts 538 along tape path assembly 118 due tofriction between tape 104 and drive belts 538. Rollers 550 hold tape 104securely against drive belts 538 as tape 104 is advanced along tape pathassembly 118. Further, covers 522 hold tape 104 flat across tape pathassembly 118 and maintain contact with drive belts 538. Tape 104 is thusdriven through instrument 100 along tape path assembly 118 via friction.

FIG. 20A is a front plan view of tape infeed 510 on tape path assembly118. FIG. 20B is a front isometric view of tape infeed 510 on tape pathassembly 118. Tape infeed 510 includes driven rollers 560, first tensionrollers 562, actuator 564, pulley 566, drive belt 568, transfer rollers570, extendable portion 572, extendable portion rollers 574, and secondtension rollers 576. Tape path assembly 118 also includes entrance ENT.Also shown in FIG. 20B is tape 104.

Tape infeed 510 is attached to tape path assembly 118 adjacent toentrance ENT. Driven rollers 560, first tension rollers 562, transferrollers 570, extendable portion rollers 574, and second tension rollers576 all comprise a pair of rollers that are parallel to each other atapproximately the width of tape 104. Driven rollers 560 comprise tackyrollers connected to tape path assembly 118 upstream of first position130. First tension rollers 562 are positioned on top of driven rollers560 and can be weighted, tensioned with springs, or otherwise compressedagainst driven rollers 560. Driven rollers 560 are driven by actuator564. In this embodiment, actuator 564 is a motor. In alternateembodiments, actuator 564 can drive driven rollers 560 with any suitablemechanism such as, for example, an electric motor, a pneumatic motor, ora hydraulic motor.

Actuator 564 is connected to driven rollers 560 via pulley 566 and drivebelt 568. Transfer rollers 570 are positioned upstream of driven rollers560 so as to be in contact with driven rollers 560. In this embodiment,transfer rollers 570 are held in tension against driven rollers 560 bysprings. In alternate embodiments, transfer rollers 570 can be held intension against driven rollers 560 with any suitable mechanism.Extendable portion 572 is positioned upstream of transfer rollers 570.Extendable portion 572 comprises extendable portion rollers 574 andsecond tension rollers 576. The rollers of second tension rollers 576are positioned on top of extendable portion rollers 574 and can beweighted, tensioned with springs, or otherwise compressed againstextendable portion rollers 574. Extendable portion rollers 574 arepositioned such that when extendable portion 572 is in a retractedposition (as shown in FIG. 20A), extendable portion rollers 574 contacttransfer rollers 570. When extendable portion 572 is in an extendedposition, extendable portion rollers 574 do not contact transfer rollers570.

When extendable portion 572 is in an extended position, tape spool 512holding tape 104 can be manually loaded into extendable portion 572.Tape 104 can then be manually advanced and fed between extendableportion rollers 574 and second tension rollers 576, which are configuredto capture and hold the leading edge of tape 104. When extendableportion 572 is in a retracted position, actuator 564 can rotate drivenrollers 560 via pulley 566 and drive belt 568. Motion from drivenrollers 560 is transferred to extendable portion rollers 574 viatransfer rollers 570. The motion from driven rollers 560 transferred toextendable portion rollers 574 advances tape 104 until tape 104 iscaptured between driven rollers 560 and first tension rollers 562, whichfurther advances tape 104 along tape path assembly 118. In this manner,tape spool 512 holding tape 104 can be manually loaded outside of theinstrument, while tape 104 can be automatically advanced within theinstrument, simplifying loading of tape spool 512 with tape 104.

FIG. 21A is a back perspective view of tape cutter 516 on tape pathassembly 118. FIG. 21B is a plan view of a front side of tape cutter 516having movable blade 580 in a retracted position. FIG. 21C is a planview of a front side of tape cutter 516 having movable blade 580 in anextended position. FIG. 21D is a plan view at entrance ENT of tape pathassembly 118 with tape cutter 516 having movable blade 580 in aretracted position. FIG. 21E is a partially transparent plan view atentrance ENT of tape path assembly 118 with tape cutter 516 havingmovable blade 580 in an extended position. Tape path assembly 118includes first position 130, driven rollers 560, first tension rollers562, and tape cutter 516. Tape cutter 516 includes sensor 578, movableblade 580, actuator 582, tape clamp 584 with tacky end 586, fixed blade588, safety guard 590, fixed blade mount 592, movable blade mount 594,and ball spring detents 596. Tape path assembly 118 also includesentrance ENT. Also shown in FIGS. 21A-21E is tape 104.

Tape cutter 516 is located immediately before first position 130 andadjacent to entrance ENT. Tape 104 can be cut with tape cutter 516 ortape 104 can pass through tape cutter 516 without being cut. Tape 104 isadvanced along tape path assembly 118, between first tension rollers 562and driven rollers 560. Sensor 578 senses when tape spool 512 (shown inFIGS. 18A-18B) is out of tape 104. As tape 104 passes between movableblade 580 and fixed blade 588, a sensor (not shown) located downstreamof tape cutter 516 can monitor the position of tape 104 to indicate toactuator 582 when a desired length of tape 104 has passed betweenmovable blade 580 and fixed blade 588. Actuator 582 can then drivemovable blade 580 upward to cut tape 104. In the embodiment shown inFIGS. 21A-21E, actuator 582 is a linear actuator. In alternateembodiments, actuator 582 can drive movable blade 580 with any suitablemechanism. Movable blade mount 594 can pivot slightly against a singlepoint. Ball spring detents 596 are positioned against a bottom end ofmovable blade 580 and give movable blade 580 a slight angle with respectto fixed blade 588. This slight angle of movable blade 580 improvescutting with movable blade 580.

Tape clamp 584 is spring-loaded and moves upward with movable blade 580.

Tape clamp 584 is configured to contact tape 104 before movable blade580. Tacky end 586 of tape clamp 584 positively holds tape 104 against abottom surface of fixed blade mount 592 while tape 104 is being cutbetween movable blade 580 and fixed blade 588. As movable blade 580 isdriven upward, spring-loaded safety guard 590 is retracted to allowmovable blade 580 to cross fixed blade 588 and cut tape 104. After tape104 has been cut, movable blade 580 retracts with tape clamp 584, andsafety guard 590 extends to contact a side surface of fixed blade mount592. In this manner, tape cutter 516 can cleanly cut tape 104 to adesired length.

FIG. 22A is a partially transparent front perspective view of liftmechanism 518. FIG. 22B is a plan view of lift mechanism 518. Liftmechanism 518 includes platform 600, shaft 604, first linkage 606,second linkage 608, actuator 610, drive pulley 612, timing pulley 614,and drive belt 616. Lift mechanism 518 is positioned under a top surfaceof tape path assembly 118. Platform 600 is raised and lowered with shaft604. Shaft 604 connects to platform 600 with first linkage 606 andsecond linkage 608.

Lift mechanism 518 is driven with actuator 610. Actuator 610 can be amotor, such as, for example, an electric motor, a pneumatic motor, or ahydraulic motor. Actuator 610 is connected to and can rotate drivepulley 612. Timing pulley 614 is positioned on shaft 604. Drive belt 616extends between and wraps around drive pulley 612 and timing pulley 614.As actuator 610 rotates drive pulley 612, drive belt 616 will move withdrive pulley 612 and rotate timing pulley 614. As timing pulley 614 isrotated, timing pulley 614 rotates shaft 604, moving first linkage 606and second linkage 608 which then move platform 600. In this manner,actuator 610 can move platform 600 up and down. Platform 600 can beactuated up and down to move parts of tape path assembly 118 up anddown.

FIG. 23A is a front plan view of lift mechanism 518 on tape pathassembly 118 in a retracted position. FIG. 23B is a front plan view oflift mechanism 518 on tape path assembly 118 in an extended position.Tape path assembly 118 includes second position 132, third position 134,fourth position 136, and lift mechanism 518. Lift mechanism 518 includesplatform 600, shaft 604, first linkage 606 (shown in FIGS. 22A-22B),second linkage 608 (shown in FIGS. 22A-22B), actuator 610, drive pulley612, timing pulley 614, and drive belt 616. Also shown in FIGS. 23A-23Bis tape level T.

Lift mechanism 518 is located underneath tape level T of tape pathassembly 118. Platform 600 is positioned underneath second position 132,third position 134, and fourth position 136. Platform 600 is attached tothird position 134. When tape 104 (not shown in FIGS. 23A-23B) isadvanced to second position 132 or fourth position 136, lift mechanism518 can be driven upward to raise second position 132 and fourthposition 136 to tape level T. Platform 600 is raised and lowered withshaft 604 extending between first linkage 606 and second linkage 608. Inalternate embodiments, platform 600 could be split to allow portionsbeneath second position 132 and fourth position 136 to be raised andlowered separately.

Lift mechanism 518 is driven by actuator 610. Actuator 610 rotates drivepulley 612, which in turn rotates timing pulley 614 on shaft 604 withbelt 616. In this manner, platform 600 can be driven upward (as seen inFIG. 23B) so that second position 132 and fourth position 136 are attape level T. This supports tape 104 as tape 104 is processed at secondposition 132 and fourth position 136.

FIG. 24 is a front perspective view of thermal units 620 and 622 on tapepath assembly 118. Tape path assembly 118 includes second position 132,third position 134, thermal unit 620, and thermal unit 622. Thermal unit620 includes thermoelectric modules (TEMs) 624. Thermal unit 622includes TEMs 626.

Thermal units 620 and 622 are positioned in tape path assembly 118.Thermal unit 620 is positioned at second position 132 and thermal unit622 is positioned at third position 134. In the embodiment shown in FIG.24, thermal unit 620 includes two TEMs 624 and thermal unit 622 includestwo TEMs 626. In alternate embodiments, thermal units 620 and 622 caninclude any number of TEMs 624 or 626, or any other mechanism capable ofheating or cooling second position 132 and third position 134. Whenheating or cooling is needed, electricity flows through TEMs 624 and 626in one direction for heating and in the other direction for cooling.This allows thermal units 620 and 622 to either cool or heat thebiological sample and reagent mixture in tape 104 in second position 132and third position 134.

FIG. 25 is a bottom view of fluid paths 630 and 640 on tape pathassembly 118. Tape path assembly 118 includes second position 132, thirdposition 134, fourth position 136, thermal unit 620, thermal unit 622,fluid path 630, inlet port 632, outlet port 634, fluid path 640, inletport 642, and outlet port 644.

Fluid paths 630 and 640 are positioned in tape path assembly 118. Fluidpath 630 is positioned at second position 132 and fluid path 640 ispositioned at third position 134. Fluid path 630 is connected to inletport 632 at a first end and to outlet port 634 at a second end. Fluidpath 640 is connected to inlet port 642 at a first end and to outletport 644 at a second end. Fluid paths 630 and 640 are cavities thatcurve back and forth under second position 132 and third position 134.Fluid from a reservoir (not shown in FIG. 26) can be delivered intofluid paths 630 and 640 through inlet ports 632 and 642, respectively.This fluid can then flow through fluid paths 630 and 640 to exchangeheat with components positioned above fluid paths 630 and 640 at secondposition 132 and third position 134, respectively. The fluid in fluidpaths 630 and 640 can then flow out through outlet ports 634 and 644,respectively. Routing the fluid underneath second position 132 and thirdposition 134 in this manner allows the space on the top surface ofsecond position 132 and third position 134 to hold components thatrequire regulated temperatures.

FIG. 26A is a partially transparent side view of retractable hold down520. FIG. 26B is a back perspective view of retractable hold down 520 ontape path assembly 118 with retractable hold down 520 in a retractedposition. FIG. 26C is a back perspective view of retractable hold down520 on tape path assembly 118 with retractable hold down 520 in anextended position. Tape path assembly 118 includes second position 132,third position 134, fourth position 136, and retractable hold down 520.Retractable hold down 520 includes roller 650, arm 652, track roller654, track 656, air cylinder 658, inlet port 660, inlet port 662, andbars 664.

Retractable hold down 520 is positioned over third position 134 and canbe moved between an extended and a retracted position. Retractable holddown 520 includes roller 650 attached to a first end of arm 652. Whenretractable hold down 520 is in an extended position, arm 652 can beextended out and down so that roller 650 can hold down tape 104 insecond position 132. A second end of arm 652 is attached to track roller654. Track roller 654 is positioned in and rolls along track 656 to movearm 652 and roller 650 between an extended and a retracted position.

Retractable hold down 520 further includes air cylinder 658. Inlet port660 and inlet port 662 are attached to air cylinder 658. Air can flowthrough inlet port 660 and inlet port 662 into air cylinder 658. A firstend of bars 664 are positioned in air cylinder 658. Bars 664 slide inand out of air cylinder 658, moving air cylinder 658 between a retractedand extended position. A second end of bars 664 is attached to arm 652.

To move retractable hold down 520 from a retracted to an extendedposition, air can flow through inlet port 660 into air cylinder 658. Asair from inlet port 660 flows into air cylinder 658 it causes bars 664to extend out of air cylinder 658. This causes track roller 654 to slidealong track 656 so that arm 652 can move to an extended position. Track656 has a first end that is positioned at an elevation that is lowerthan the elevation of a second end of track 656. As track roller 654moves from the first end to the second end of track 656, the second endof arm 652 will be driven upward. This in turn causes the first end ofarm 652 to be driven down. This motion can force roller 650 on the firstend of arm 652 down against tape 104 and/or second position 132 of tapepath assembly 118.

To move retractable hold down 520 from an extended position to aretracted position, air can flow through inlet port 662 into aircylinder 658. As air from inlet port 662 flows into air cylinder 658 itcauses bars 664 to retract back into air cylinder 658. This causes trackroller 654 to slide along track 656 so that arm 652 can move to aretracted position. This motion will cause roller 650 on the first endof arm 652 to move up from tape 104 and/or second position 132 of tapepath assembly 118.

When a leading edge, positioning hole, or other identifying mark of tape104 (not shown) is detected by a sensor positioned along tape pathassembly 118, retractable hold down 520 can extend roller 650 to holddown the leading edge or a middle portion of tape 104. Tape 104 can beprocessed when roller 650 of retractable hold down 520 is extended.After tape 104 is processed, retractable hold down 520 can retract andallow tape 104 to be further processed or advanced to third position134. For example, roller 650 can be extended to hold down tape 104 atsecond position 132 while tape 104 is being dispensed into. After tape104 has been dispensed into, roller 650 can be retracted and a sealingoperation can be performed. In this manner, multiple operations, such asdispensing and sealing, can be performed on the same portion of tape 104at the same location reducing the overall size of instrument 100.

FIG. 27 is a perspective view of rewind assembly 108. Rewind assembly108 can be attached to cart assembly 101 and aligned with tape pathassembly 118 to accumulate processed tape leaving tape path assembly 118(see FIGS. 1B-1C). Rewind assembly 108 includes mounting bracket 670,motor 672, shaft 674, spool 676, retainer clips 678, and spool retainer680.

Mounting bracket 670 attaches rewind assembly 108 to cart assembly 101(see FIGS. 1B-1C). Motor 672 is attached to shaft 674. Shaft 674mechanically engages spool 676. Spool 676 is secured on shaft 674 withspool retainer 680. Rotation of motor 672 is synchronized with movementof tape 104 through tape path assembly 118. Once tape 104 begins to exittape path assembly 118, tape 104 is attached to spool 676 using tape oranother attaching means. Rotation of motor 672 causes spool 676 torotate and accumulate tape 104 on spool 676. After processing of allarrays of tape 104 is complete, tape 104 is secured to spool 676 withretainer clips 678. Spool 676 can be removed from rewind assembly 108 byremoving spool retainer 680 and sliding spool 676 off of shaft 674.

Dispensing Assembly

FIG. 28 is an isometric view of instrument 100 with dispensing assembly114. Dispensing assembly 114 includes gantry x-axis track 702, gantryy-axis track 704, dispensing enclosure 706, and dispensing head 708.Gantry x-axis track 702 includes actuator 710, drive belt 712, and cablecarrier 714. Gantry y-axis track 704 includes actuator 716, drive belt718, and cable carrier 720. Actuator 710 is connected to drive belt 712,and actuator 716 is connected to drive belt 718.

Gantry x-axis track 702 and gantry y-axis track 704 allow dispensingenclosure 706 and dispensing head 708 to move in the x and y directionswithin instrument 100. Gantry y-axis track 704 is connected to cablecarrier 714. Dispensing enclosure 706 sits on top of gantry y-axis track704 and is connected to dispensing head 708 and cable carrier 720. Cablecarrier 714 and cable carrier 720 guide wiring and tubing going todispensing enclosure 706 and dispensing head 708. Dispensing head 708sits underneath gantry y-axis track 704. Dispensing enclosure 706 anddispensing head 708 can move simultaneously along gantry y-axis track704.

In order to move gantry y-axis track 704 with dispensing enclosure 706and dispensing head 708 in the x direction along gantry x-axis track702, actuator 710 drives drive belt 712. Drive belt 712 moves gantryy-axis track 704 along gantry x-axis track 702. Cable carrier 714includes a stationary end that does not move and an end attached togantry y-axis track 704 that moves along with gantry y-axis track 704.Cable carrier 714 holds all cabling and tubing required for dispensingassembly 114 properly aligned when gantry y-axis track 704 moves alonggantry x-axis track 702. In the embodiment shown, actuator 710 is aservo motor, and the shaft rotation position of the servo motor iscontrolled by the control systems of instrument 100, including anindustrial PC and associated interface cards in electronic assembly 124.

In order to move dispensing enclosure 706 and dispensing head 708 in they direction along gantry y-axis track 704, actuator 716 drives drivebelt 718. Drive belt 718 moves dispensing enclosure 706 and dispensinghead 708 along gantry y-axis track 704. Cable carrier 720 includes astationary end that does not move and an end attached to dispensingenclosure 706 that moves along with dispensing enclosure 706. Cablecarrier 720 keeps all cables and tubes required for dispensing assembly114 properly aligned when dispensing enclosure 706 and dispensing head708 move in the y direction along gantry y-axis track 704. In theembodiment shown, actuator 710 is a servo motor, and the shaft rotationposition of the servo motor is controlled by the control systems ofinstrument 100, including an industrial PC and associated interfacecards in electronic assembly 124.

Dispensing assembly 114 aspirates a sample or a reagent from a sampleplate or a reagent plate and dispenses the sample or reagent into thewells of tape 104 positioned at second position 132 of tape pathassembly 118. Dispensing assembly 114 moves dispensing enclosure 706 anddispensing head 708 in the x direction and in the y direction alonggantry x-axis track 702 and gantry y-axis track 704 in order to positiondispensing enclosure 706 and dispensing head 708 above a sample plate orreagent plate. Dispensing assembly 114 then extends dispensing head 708in the z direction in order to aspirate a sample or reagent from thesample plate or reagent plate. Dispensing assembly 114 subsequentlyretracts dispensing head 708 in the z direction and again movesdispensing enclosure 706 and dispensing head 708 in the x direction andin the y direction in order to position dispensing enclosure 706 anddispensing head 708 above tape 104. Dispensing assembly 114 then extendsdispensing head 708 in the z direction in order to dispense the sampleor reagent into the wells of tape 104. While aspirating or dispensing,if necessary, dispensing assembly 114 can move dispensing head 708 inthe x direction, y direction, and z direction to re-position dispensinghead 708.

FIG. 29 is a schematic view of dispensing assembly 114 seen in FIG. 28.Dispensing assembly 114 includes gantry x-axis track 702, gantry y-axistrack 704, dispensing enclosure 706, and dispensing head 708. Gantryx-axis track 702 includes actuator 710, drive belt 712, and cablecarrier 714. Gantry y-axis track 704 includes actuator 716, drive belt718, and cable carrier 720. Dispensing enclosure 706 includes pressurereservoir 722, metering pump 724, manifold 726, system fluid supply andwaste 728, and electronics 730. Dispensing head 708 includes contactdispensing unit 732 and non-contact dispensing unit 734.

Dispensing assembly 114 combines multiple dispensing technologies into asingle head by providing both contact and non-contact dispensing withdispensing head 708. Gantry x-axis track 702 and gantry y-axis track 704provide shared x- and y-axes for dispensing head 708, which reduces costand conserves space within instrument 100.

FIG. 30 is a perspective view of gantry y-axis track 704, dispensingenclosure 706, and dispensing head 708 of dispensing assembly 114 seenin FIG. 28. Gantry y-axis track 704 includes actuator 716, drive belt718, and cable carrier 720. Dispensing enclosure 706 includes manifold726 with channels 736. Dispensing head 708 includes contact dispensingunit 732 with pipette tips 738 and non-contact dispensing unit 734 withjet tips 740 and valves 742. Tubes 744 connect non-contact dispensingunit 734 to dispensing enclosure 706. Tubes 744 are attached to jet tips740 and to channels 736 of manifold 726.

As shown in FIGS. 28-30, contact dispensing unit 732 dispenses a liquidinto tape 104 (not shown). In an alternative embodiment, contactdispensing unit 732 can dispense a liquid into a plate with a pluralityof wells, such as a microtiter plate. In an alternative embodiment,contact dispensing unit 732 may dispense onto a flat surface. Contactdispensing unit 732 can be a parallel channel pipettor. Contactdispensing unit 732 aspirates and dispenses liquid with pipette tips738. The liquid can be a biological sample. In an alternativeembodiment, the liquid can be a reagent. Contact dispensing unit 732 mayinclude a single pipette tip 738. In alternative embodiments, contactdispensing unit 732 may include any number of pipette tips 738 including96 pipette tips 738 or 384 pipette tips 738. Contact dispensing unit 732dispenses a liquid while the liquid is still in tips 740. Tips 740 comeinto contact with the wells into which the liquid is dispensed.

Non-contact dispensing unit 734 dispenses a liquid into tape 104. In analternative embodiment, non-contact dispensing unit 734 can dispense aliquid into a plate with a plurality of wells, such as a microtiterplate. In an alternative embodiment, non-contact dispensing unit 734 maydispense onto a flat surface. Non-contact dispensing unit 734 can be anindependent channel non-contact jet dispenser. Non-contact dispensingunit 732 aspirates and dispenses liquid with jet tips 740. The liquidcan be a reagent. In an alternative embodiment, the liquid can be abiological sample. Non-contact dispensing unit 732 may include a singlejet tip 740. In alternative embodiments, non-contact dispensing unit 732may include any number of jet tips 740, including two, four, eight, orsixteen jet tips 740. When non-contact dispensing unit 732 dispenses aliquid, the liquid separates from jet tips 740 and only the liquid comesinto contact with the wells into which the liquid is dispensed.

In order to separate a liquid from jet tips 740, metering pump 724 ofdispensing enclosure 706 pressurizes pressure reservoir 722, tubes 744and jet tips 740 to a desired pressure based on dispense fluid viscosityand a desired dispensing volume. Pressure reservoir 722 is used to storepressure created by metering pump 724. Pressure reservoir 722 provides aconstant pressure for dispensing. In order to dispense the liquid,electronics 730 actuates valves 742 to open valves 742, and the pressurein tubes 744 allows the liquid to shoot out from jet tips 740. In theembodiment shown, valves 742 are solenoid valves. Valves 742 may beopened one at a time in order to dispense liquid from jet tips 740 oneat a time. In an alternative embodiment, valves 742 may be openedsimultaneously in order to dispense liquid from jet tips 740 at the sametime. As stated above in reference to FIG. 28, dispensing enclosure 706and dispensing head 708 are connected and move simultaneously alonggantry y-axis track 704. This prevents bending and stretching of tubes744 during dispensing, thereby minimizing pressure fluctuations withintubes 744. Reducing pressure fluctuations in tubes 744 improves thedispensing accuracy of non-contact dispensing unit 734, especially atlow dispensing volumes such as 800 nanoliters.

FIG. 31A is an isometric view of dispensing head 708 with contactdispensing unit 732 in an extended position and non-contact dispensingunit 734 with jet tips 740 in a retracted position. FIG. 31B is anisometric view of dispensing head 708 with contact dispensing unit 732in a retracted position and non-contact dispensing unit 734 in anextended position. Non-contact dispensing unit 734 includes jet tips 740and valves 742. In addition to contact dispensing unit 732 andnon-contact dispensing unit 734, dispensing head 708 includes firstz-axis track 746 with rails 748, spring 750, and actuator 752.Dispensing head 708 also includes second z-axis track 754 with rail 756,spring 758 (shown in FIG. 31C), and actuator 760. Actuator 752 movescontact dispensing unit 732 in the z direction along rails 748. Actuator760 moves non-contact dispensing unit 734 in the z direction along rail756.

FIG. 31C is a partially transparent perspective view of first z-axistrack 746 and second z-axis track 754 of dispensing head 708 seen inFIGS. 31A-31B. Non-contact dispensing unit 734 with jet tips 740 isattached to second z-axis track 754. First z-axis track 746 includesrails 748, spring 750, actuator 752, attachment plate 762, fine pitchadjustment mechanism 764, pivot bolt 766, and identification mechanism768. Second z-axis track 754 includes rail 756, spring 758, and actuator760.

As shown in FIGS. 30, 31A, 31B, and 31C, in the embodiment shown, firstz-axis track 746 is attached to gantry y-axis track 704. Contactdispensing unit 732 is attached to and moves along first z-axis track746, and non-contact dispensing unit 734 is attached to and moves alongsecond z-axis track 754. In the embodiment shown, second z-axis track754 is attached to contact dispensing unit 732 such that second z-axistrack 754 and non-contact dispensing unit 734 move in the z directionwhen contact dispensing unit 732 moves in the z direction along firstz-axis track 746. In an alternative embodiment, second z-axis track 754can be attached to gantry y-axis track 704 such that non-contactdispensing unit 734 moves in the z direction only along second z-axistrack 754, independent from the z-axis motion of contact dispensing unit732. In an another alternative embodiment, where second z-axis track 754is attached to gantry y-axis track 704, first z-axis track 746 can beattached to non-contact dispensing unit 734 such that first z-axis track746 and contact dispensing unit 732 move in the z direction whennon-contact dispensing unit 734 moves in the z direction along secondz-axis track 754. In an alternative embodiment, each individual valve742 attached to a corresponding jet tip 740 can be mounted to anindependent z-axis track to enable each individual valve 742 andcorresponding jet tip 740 to move independently in the z direction.

Contact dispensing unit 732 attaches to attachment plate 762 of firstz-axis track 746. Prior to attaching contact dispensing unit 732, finepitch adjustment mechanism 764 rotates attachment plate 762 around pivotbolt 766 in order to adjust the angle of attachment plate 762. Thisensures that contact dispensing unit 732 is attached to attachment plate762 such that pipette tips 738 are aligned and level with the matrix ofwells of tape 104, sample plate, or reagent plate for aspiration anddispensing.

When contact dispensing unit 732 is in an extended position, spring 750is compressed. In the event of a loss of power to actuator 752, spring750 will hold the z direction position of contact dispensing unit 732 orretract contact dispensing unit 732 along first z-axis track 746. Thisprevents damage to pipette tips 738 and serves as a safety mechanism inthe event a user is interacting with dispensing head 708 insideinstrument 100. In alternative embodiments, a gas shock, alternate typeof spring, or friction limit via a gear train can be used. Second z-axistrack 754 include spring 758, which functions in the same manner asspring 750 in order to hold the z direction position of non-contactdispensing unit 734 or retract non-contact dispensing unit 734 in theevent of a loss of power to actuator 760. This prevents damage to jettips 740 and serves as a safety mechanism in the event an operator isinteracting with dispensing head 708 inside instrument 100.

In order to aspirate and dispense, contact dispensing unit 732 movesalong first z-axis track 746 to an extended position (FIG. 31A).Non-contact dispensing unit 734 remains in a retracted position alongsecond z-axis track 754. In order to aspirate and dispense, non-contactdispensing unit 734 moves along second z-axis track 754 into an extendedposition (FIG. 31B) such that jet tips 740 extend past contactdispensing unit 732. Contact dispensing unit 732 can be in an extendedposition or a retracted position when non-contact dispensing unit 734aspirates and dispenses. During or prior to aspiration or dispensing,identification mechanism 768 can read an identifier, such as a barcode,off of tape 104, a sample plate, or a reagent plate to identify thecontents and configuration of tape 104, the sample plate, or the reagentplate. In one embodiment, identification mechanism 768 can be a camera.In an alternative embodiment, identification mechanism 768 can be aradio frequency identification reader used in combination with radiofrequency identification tags on or in tape 104, a sample plate, or areagent plate to identify the configuration and contents of tape 104,the sample plate, or the reagent plate.

FIG. 32A is a transparent isometric view of dispensing enclosure 706 ofdispensing assembly 114 seen in FIGS. 28-30. FIG. 32B is a perspectiveview of dispensing enclosure 706. FIGS. 32A-32B are transparent to showthe components enclosed in dispensing enclosure 706. Dispensingenclosure 706 includes pressure reservoir 722, metering pump 724,manifold 726 with channels 736, system fluid supply and waste 728,electronics 730, pressure reservoir valve 770, and pressure sensor 772.System fluid supply and waste 728 includes supply port 774, waste port776, and system fluid valve 778. Supply port 774 is connected to asystem fluid supply and waste port 776 is connected to a wastereceptacle.

FIG. 33 is a schematic diagram of non-contact dispensing components ofdispensing enclosure 706 and the dispensing head 708 seen in FIGS.31A-31C and 32A-32B. Dispensing enclosure 706 includes pressurereservoir 722, metering pump 724, manifold 726 with channels 736, systemfluid supply and waste 728, pressure reservoir valve 770, pressuresensor 772, check valve 780, and filter 782. System fluid supply andwaste 728 includes supply port 774, waste port 776, system fluid valve778, and check valve 784. Non-contact dispensing unit 734 includes jettips 740 and valves 742. Tubes 744 connect non-contact dispensing unit734 to dispensing enclosure 706. Tubes 744 are attached to jet tips 740and to channels 736 of manifold 726.

As shown in FIGS. 32A-32B and FIG. 33, dispensing enclosure 706 isconnected to jet tips 740 with tubes 744. Tubes 744 are connected tomanifold 726 through channels 736, and each of tubes 744 is connected toeach of jet tips 740. Pressure sensor 772 measures the pressure inmanifold 726, which is the same as the pressure in tubes 744. Valves 742open and close jet tips 740. Electronics 730 provides power to andassists in the control of all components of dispensing enclosure 706 anddispensing head 708. In the embodiment shown, electronics 730 is aprinted circuit board.

Metering pump 724 supplies the system fluid flow needed to wash andpressurize non-contact dispensing system 36 and dispensing enclosure706. Metering pump 724 is connected to pressure reservoir valve 770 andsystem fluid valve 778. Supply port 774 is connected to a system fluidsupply and waste port 776 is connected to a waste receptacle. Systemfluid, such as water, enters dispensing enclosure 706 through supplyport 774 and system waste fluid leaves through waste port 776. Systemfluid valve 778 controls system fluid into and waste flow out ofdispensing enclosure 706 and through metering pump 724. Pressurereservoir 722 is connected to pressure reservoir valve 770. Pressurereservoir valve 770 controls system fluid flow into and out of pressurereservoir 722. Pressure sensor 772 measures the pressure in pressurereservoir 722 in order to determine whether a desired pressure inpressure reservoir 722 has been reached. Check valve 780 allows ambientair into pressure reservoir 722 if the pressure in pressure reservoir722 drops below atmospheric pressure. Filter 782 prevents any unwantedparticles from entering pressure reservoir 722. Electronics 730 providespower to and controls all components of dispensing enclosure 706 anddispensing head 708 except for actuators. In the embodiment shown,electronics 730 is a printed circuit board.

In order to begin operation of dispensing enclosure 706 along withnon-contact dispensing unit 734, non-contact dispensing unit 734 ismoved into a wash position. Pressure reservoir valve 770 is closed andvalves 742 and system fluid valve 778 are opened. Metering pump 724 isthen run forward in order to pump system fluid through supply port 774,through check valve 784, into manifold 726, through channels 736, intotubes 744, and through jet tips 740 in order to purge any air or wastein jet tips 740. Jet tips 740 and tubes 744 are now filled with systemfluid and valves 742 are closed.

Non-contact dispensing unit 734 is then moved into an aspirationposition above a reagent plate. Valves 742 are opened and closed one ata time and metering pump 724 is run backwards in order to aspirate anair gap into each of jet tips 740. In this embodiment, the air gap isapproximately 20,000 nanoliters. Jet tips 740 are subsequently loweredinto the wells of the reagent plate, valves 742 are opened and closedone at a time, and metering pump 724 is run backwards in order toaspirate a reagent into jet tips 740. In this embodiment, jet tips 740aspirate between 80,000 and 700,000 nanoliters of reagent into each ofjet tips 740. In alternate embodiments, jet tips 740 can aspirate otheramounts of reagent based on the size of tubes 744. The air gap preventssystem fluid and the reagent from mixing. Once the reagent is aspiratedinto one or more of jet tips 740, pressure reservoir valve 770 isopened, metering pump 724 is run forward, and system fluid is pumpedinto pressure reservoir 722 through the bottom of pressure reservoir722. This creates pressure by compressing the air above the system fluidin pressure reservoir 722 and pressurizing the system fluid in tubes744, the air gap in between the system fluid and the reagent, and thereagent in tubes 744. Metering pump 724 is run until a desired pressureis reached, the pressure corresponding to the viscosity and the amountof reagent needed for dispensing. Pressure sensor 772 measures thepressure in pressure reservoir 722 and the components of manifold 726 inorder to determine when the desired pressure is reached.

Non-contact dispensing unit 734 is then moved into a dispensing positionabove tape 104 or above a plate. Each of valves 742 is triggered byelectronics 730 above a desired well. Once each of valves 742 istriggered, the pressure in tubes 744 and jet tips 740 causes the reagentto shoot out of each of jet tips 740 and into the wells of tape 104.Non-contact dispensing unit 734 is moved in the x and y directions alongthe matrix of wells of tape 104 and valves 742 are triggered repeatedlyin order to dispense the reagent into each of the wells of tape 104. Jettips 740 move across tape 104 in the x and y directions duringdispensing. In the embodiment shown, jet tips 740 move continuously anddispense without having to stop above each well of tape 104. Non-contactdispensing unit 734 can dispense between 100 and 3,000 nanoliters ofreagent. Valves 742 can be triggered one at a time in order to dispensethe reagent from each of jet tips 740 one at a time. In an alternativeembodiment, valves 742 can be triggered simultaneously in order todispense reagent into multiple wells at once. Once the reagent isdispensed into the wells of tape 104, non-contact dispensing unit 734can be moved back into a wash position and the process can be repeated.

As shown in FIGS. 28-33, dispensing head 708 can move along gantryx-axis track 702 and gantry y-axis track 704 to aspirate and dispense areagent and/or a biological sample with contact dispensing unit 732 andnon-contact dispensing unit 734 in a variety of sequences. In oneembodiment, dispensing head 708 moves along gantry x-axis track 702 andgantry y-axis track 704 to a first aspiration position where contactdispensing unit 732 aspirates a first liquid into at least one ofpipette tips 738. Dispensing head 708 subsequently moves to a secondaspiration position where non-contact dispensing unit 734 aspirates asecond liquid into at least one of jet tips 740. Dispensing head 708then moves to a first dispensing position where contact dispensing unit732 dispenses the first liquid with at least one of pipette tips 738.Finally dispensing head 708 moves to a second dispensing position wherenon-contact dispensing unit 734 dispenses the second liquid with atleast one of jet tips 740. This aspirating and dispensing sequenceminimizes evaporation of the first and second liquids during thesequence. In alternative embodiment that also minimizes evaporation ofthe first and second liquids, the sequence can be such that non-contactdispensing unit 734 aspirates, contact dispensing unit 732 aspirates,non-contact dispensing unit 734 dispenses, and contact dispensing unit732 dispenses.

In another alternative embodiment, non-contact dispensing unit 734aspirates, contact dispensing unit 732 aspirates, contact dispensingunit 732 dispenses, and non-contact dispensing unit 734 dispenses. Thissequence minimizes the time a liquid is in pipette tips 738 of contactdispensing unit 732 before the liquid is dispensed. In anotheralternative embodiment, contact dispensing unit 732 aspirates,non-contact dispensing unit 734 aspirates, non-contact dispensing unit734 dispenses, and contact dispensing unit 732 dispenses. This sequenceminimizes the time a liquid is in jet tips 740 of non-contact dispensingunit 734 before the liquid is dispensed.

Tape Sealing Assembly

FIG. 34A is an isometric view of instrument 100 with tape sealingassembly 120. Tape sealing assembly 120 includes applicator 800 andlocking mechanism 802. Seal web 804 is secured to seal assembly 120 withlocking mechanism 802. FIG. 34B is a perspective view of seal web 804with seals 106 on backer 806. Tape sealing assembly 120 peels seals 106off of backer 806 of seal web 804. Applicator 800 of tape sealingassembly 120 seals tape 104 with seals 106 after a biological sample anda reagent have been dispensed into tape 104. Seals 106 contain thebiological sample and reagent mixture in tape 104 and prevent spillage,evaporation, and contamination of the biological sample and reagentmixture in tape 104.

FIG. 35 is a perspective view of tape sealing assembly 120 positionedadjacent to tape path assembly 118. Tape path assembly 118 includesfirst position 130, second position 132, third position 134, and fourthposition 136. Tape sealing assembly 120 includes head 808. Tape sealingassembly 120 can be moved in the y direction normal to tape pathassembly 118 and in the x direction parallel to tape path assembly 118.Thus, tape sealing assembly 120 can be positioned adjacent to tape pathassembly 118, with head 808 positioned at second position 132. Tapesealing assembly 120 seals tape 104 at second position 132 after thebiological sample and reagent are dispensed.

FIG. 36A is a top view of tape sealing assembly 120 within instrument100. FIGS. 36B and 36C are perspective views of tape sealing assembly120. Tape sealing assembly 120 includes x-axis drive mechanism 810 withactuator 812 and drive belt 814, y-axis drive mechanism 816 withactuator 818 and drive belt 820, x-axis stage 822, x-axis rails 824,y-axis stage 826, and y-axis rails 828. X-axis drive mechanism 810 isconnected to x-axis stage 822. Y-axis drive mechanism 816 is connectedto y-axis stage 826. X-axis stage 822 is installed on x-axis rails 824,and y-axis stage 826 is installed on y-axis rails 828. Y-axis rails 828are installed on x-axis stage 822.

X-axis drive mechanism 810 and y-axis drive mechanism 816 move tapesealing assembly 120 in the x and y directions in order to align tapesealing assembly 120 with tape path assembly 118 such that seal 106 canbe properly applied to tape 104. To move tape sealing assembly 120 inthe x direction, actuator 812 drives drive belt 814, transferring motionto x-axis stage 822 and moving x-axis stage across x-axis rails 824. Inthe embodiments shown in FIGS. 36A-36C, actuator 812 is a motor. Inalternate embodiments, actuator 812 can drive drive belt 814 with anysuitable mechanism such as, for example, an electric motor, a pneumaticmotor, or a hydraulic motor. To move tape sealing assembly 120 in the ydirection, actuator 818 drives drive belt 820, transferring motion toy-axis stage 826 and moving y-axis stage 826 across y-axis rails 828. Inthe embodiment shown in FIGS. 36A-36C, actuator 818 is a motor. Inalternate embodiments, actuator 818 can drive drive belt 820 with anysuitable mechanism such as, for example, an electric motor, a pneumaticmotor, or a hydraulic motor.

FIG. 37A is an isometric view of a portion of tape sealing assembly 120.FIG. 37B is a side view of tape sealing assembly 120 with threading pathB. Tape sealing assembly 120 includes seal web 804, head 808, spoolholder 830 with locking mechanism 802, sensor 834, peel plate 836 withbottom edge 838, backer take-up mechanism 840, lever 862, and slipclutch 874. Backer take-up mechanism 840 includes in-feed guide 842, topguide 844, out-feed guide 846, drive roller 848, friction roller 849,tension bar 856, tension spring 857, shaft 858, shaft actuator 860, andfixed idler 864. Seal web 804 is installed on spool holder 830 andthreaded through tape sealing assembly 120 along threading path B.

Prior to threading seal web 804 through tape sealing assembly 120, sealweb 804 is placed on spool holder 830 and locking mechanism 802 securesseal web 804 in tape sealing assembly 120. In the embodiments shown inFIGS. 37A-37B, locking mechanism 802 is a knob locking mechanism (shownin further detail in FIGS. 39A-39B). In alternate embodiments, lockingmechanism 802 can secure seal web 804 with any suitable mechanism, suchas a cam lock and lever. Before seal web 804 is manually threadedthrough tape sealing assembly 120, a number of seals 106 can be removedsuch that only backer 806 is manually threaded.

Once seal web 804 is secured on spool holder 830, lever 862 is rotatedclockwise approximately ninety degrees to open threading path B (seeFIGS. 38B-38C for more detail), and seal web 804 can be manuallythreaded along threading path B through tape sealing assembly 120. Sealweb 804 is first routed across peel plate 836 and around bottom edge 838of peel plate 836. Seal web 804 enters backer take-up mechanism 840through in-feed guide 842. Seal web 804 is manually advanced pastin-feed guide 842, top guide 844, out-feed guide 846, and out the backof backer take-up mechanism 840. Seal web 804 is manually advanced pastfixed idler 864 and fastened to shaft 858. Threading path B is thenclosed by rotating lever 862 counter-clockwise, returning lever 862 toits original position (see FIGS. 38A-38B for more detail). Whenthreading path B is closed, friction roller 849 clamps backer 806against drive roller 848. Tension spring 857 determines the amount ofclamping force. In one embodiment, seal web 804 can be fastened to adisposable take-up core (not shown) attached to shaft 858. The use of adisposable take-up core simplifies removal of backer 806 from tapesealing assembly 120 after seals 106 have been removed from seal web804, leaving backer 806 wound around the disposable take-up core (notshown).

Once seal web 804 has been manually threaded through tape sealingassembly 120, seal web 804 can be automatically advanced through tapesealing assembly 120 along threading path B. To automatically advanceseal web 804, actuator 850 drives drive roller 848 to advance seal web804 between friction roller 849 and drive roller 848. Slip clutch 874 ofspool holder 830 maintains a desired level of tension in seal web 804over bottom edge 838 of peel plate 836 and along threading path Bbetween spool holder 830, drive roller 848, and friction roller 849.After tape sealing assembly 120 has automatically advanced seal web 804,shaft actuator 860 rotates shaft 858 to take up slack created in sealweb 804 along threading path B between shaft 858 and drive roller 848and friction roller 849. Shaft 858 can wind or rewind backer 806. Asbacker 806 from seal web 804 is wound around shaft 858, fixed idler 864can come into contact with seal web 804. As seal web 804 progressesthrough tape sealing assembly 120 and seals 106 are removed from backer806, backer 806 is wound around shaft 858. Backer 806 wound around shaft858 can be disposed once shaft 858 is full.

As backer take-up mechanism 840 automatically advances seal web 804,sensor 834 detects the location of seal 106 on seal web 804 via sensorpath S. Sensor 834 signals backer take-up mechanism 840 to stopadvancing seal web 804 when seal 106 is positioned on peel plate 836.Bottom edge 838 of peel plate 836 can have a small radius to facilitateseal peeling when tape sealing assembly 120 is automatically advancingseal web 804. As seal web 804 moves across peel plate 836 and passesaround bottom edge 838, sensor 834 signals backer take-up mechanism 840to stop advancing seal web 804 just before seal 106 moves past bottomedge 838 of peel plate 836 and begins to separate from backer 806.Bottom edge 838 of peel plate 836 is angled such that when seal 106moves past bottom edge 838, a leading edge of seal 106 is separated frombacker 806. In alternate embodiments, a second sensor may be used tosense when a leading edge of seal 106 has passed by bottom edge 838thereby indicating that the leading edge of seal 106 has separated frombacker 806.

FIG. 38A is a perspective view of backer take-up mechanism 840. FIG. 38Bis a side view of backer taker-up mechanism 840 with friction roller 849in a closed position. FIG. 38C is a side view of backer taker-upmechanism 840 with friction roller 849 in an open position. Backertake-up mechanism 840 includes in-feed guide 842, top guide 844, mount845, out-feed guide 846, drive roller 848, friction roller 849, actuator850, pulley 852, drive belt 854, tension bar 856, tension spring 857,lever 862, and cam 863.

While seal web 804 is automatically advanced through backer take-upmechanism 840, seal web 804 is pinched between friction roller 849 anddrive roller 848 such that friction roller 849 rotates at the same rateas drive roller 848. In order to allow seal web 804 to be manuallythreaded through threading path B (shown in FIG. 37B), lever 862 can berotated approximately ninety degrees clockwise to rotate friction roller849 away from drive roller 848. This moves friction roller 849 from theclosed position seen in FIG. 38B to the open position seen in FIG. 38C.Once friction roller 849 is in an open position, seal web 804 can bemanually threaded through threading path B, passing by in-feed guide 842and top guide 844, between friction roller 849 and drive roller 848, andover out-feed guide 846. Lever 862 can then be rotated counter-clockwiseto rotate friction roller 849 back to a closed position in which sealweb 804 is pinched between drive roller 848 and friction roller 849.

Friction roller 849 is opened and closed by rotation of lever 862. Lever862 is attached to cam 863 and tension bar 856 such that when lever 862is rotated, cam 863 rotates as well. When lever 862 is rotatedclockwise, cam 863 pushes against mount 845, rotating tension bar 856clockwise to the position in FIG. 38C. The clockwise rotation of tensionbar 856 moves friction roller 849 away from drive roller 848 such thatfriction roller 849 no longer contacts drive roller 848. This makes itpossible for seal web 804 to be manually fed into backer take-upmechanism 840. After seal web 804 has been manually fed into backertake-up mechanism 840, lever 862 can be rotated counter-clockwise torotate cam 863 in the opposite direction to return tension bar 856 tothe position in FIG. 38B. This allows spring 857, which pulls on tensionbar 856, to pull friction roller 849 into drive roller 848 until sealweb 804 is pinched between drive roller 848 and friction roller 849 witha determined amount of force. This makes it possible to automaticallyadvance seal web 804.

FIGS. 39A-39B are cross-sectional views of spool holder 830, withlocking mechanism 802 in an unlocked position in FIG. 39A, and lockingmechanism 802 in a locked position in FIG. 39B. Spool holder 830includes locking mechanism 802, compression piece 866, rubber roller868, screw 870, spool 872, and slip clutch 874.

In order to prevent spool 872 from rotating independently of spoolholder 830, spool holder 830 includes locking mechanism 802. Lockingmechanism 802 is connected to compression piece 866, which is connectedto rubber roller 868, such that when locking mechanism 802 is locked,locking mechanism 802 presses into compression piece 866, which in turncompresses rubber roller 868. Locking mechanism 802 can be locked orunlocked by manually rotating locking mechanism 802 around the end ofscrew 870. Locking mechanism 802 can be locked part way, therebyproviding for a variable pressure on rubber roller 868 and thus avariable pressure on spool 872. When locking mechanism 802 is in thelocked position, the maximum pressure is exerted by rubber roller 868 onspool 872. When locking mechanism 802 is in the unlocked position, nopressure is exerted by rubber roller 868 on spool 872. When lockingmechanism 802 is in a partially locked position, a partial amount ofpressure is exerted by rubber roller 868 on spool 872. In this manner,spool 872 rotates with rubber roller 868 as seal web 804 isautomatically advanced through tape sealing assembly 120. Slip clutch874 is adjustable to maintain a desired tension in backer 806 alongthreading path B (shown in FIG. 37B) as seal web 804 is manually orautomatically advanced through tape sealing assembly 120.

FIG. 40 is a partially transparent perspective view of applicator 800 oftape sealing assembly 120. FIG. 41 is a bottom view of pad 876 ofapplicator 800. Applicator 800 includes head 808, pad 876 having vacuumholes 878, shaft 880, actuator 882, shaft 884, drive belt 886, pulleys888, and vacuum chambers 890. Head 808 is connected to and rotatesaround shaft 880. Head 808 is connected to drive belt 886. Drive belt886 wraps around pulleys 888 and shaft 884. Shaft 884 is connected toactuator 882. Head 808 includes applicator vacuum chambers 890, whichform vacuum holes 878 in applicator pad 876. The convex face of head 808is lined with pad 876, which can be made from vulcanized rubber tofacilitate compression when head 808 presses seal 106 onto tape 104. Inorder to move head 808, actuator 882 drives shaft 884. Shaft 884 rotateshead 808 around shaft 880 via drive belt 886 and pulleys 888. Head 808rotates around shaft 880 to peel seal 106 from seal web 804 and pressseal 106 onto tape 104.

FIGS. 42A-42B are partially transparent perspective views of a portionof tape sealing assembly 120 removing seal 106 from backer 806 of sealweb 804. Seal 106 is in a peel position in FIG. 42A. Seal 106 iscompletely removed from backer 806 in FIG. 42B. Tape sealing assembly120 includes applicator 800 (shown fully in FIG. 40), peel plate 836with bottom edge 838 (seen in FIG. 37B), and backer take-up mechanism840 with in-feed guide 842. Applicator 800 includes head 808 with firstedge 892 and second edge 894, pad 876 with vacuum holes 878 (shown inFIGS. 40-41), shaft 880, and vacuum chambers 890 (shown in FIG. 40).

Applicator 800 moves head 808 such that pad 876 faces peel plate 836with first edge 892 of head 808 near a leading edge of seal 106 in aposition to be peeled. Head 808 rotates around shaft 880 at the samerate that seal web 804 is advanced by backer take-up mechanism 840.Vacuum chambers 890 can be activated in stages such that vacuum chambers890 are activated gradually from first edge 892 to second edge 894 ofhead 808 as seal 106 is peeled from backer 806. Vacuum chambers 890 canbe activated only for the portion of seal 106 peeled and in contact withpad 876. When seal 106 is completely removed from backer 806, all ofvacuum chambers 890 can be activated. When seal 106 is completelyremoved from backer 806 and fully captured by head 808, head 808 movesinto a position facing down toward tape 104.

Backer take-up mechanism 840 advances seal web 804 at the same rate asapplicator 800 rotates head 808 around shaft 880 to pick up seal 106from seal web 804. In this manner, backer take-up mechanism 840 canautomatically advance seal web 804 around peel plate 836 and throughin-feed guide 842, and backer take-up mechanism 840 can work inconjunction with applicator 800 to peel seal 106 from seal web 804.

FIGS. 43A-43B are side views of tape sealing assembly 120 applying seal106 to tape 104 at second position 132 on tape path assembly 118. FIG.43A is a side view of tape sealing assembly 120 just before seal 106 isapplied. FIG. 43B is a side view of tape sealing assembly 120 just afterseal 106 is applied. Tape sealing assembly 120 includes head 808, x-axisstage 822, x-axis rails 824, y-axis stage 826, and y-axis rails 828. Pad876 is positioned on head 808 and includes vacuum holes 878 (shown inFIGS. 40A-40B), vacuum chambers 890 (shown in FIGS. 40A-40B), first edge892, and second edge 894.

In order to apply seal 106 to tape 104, y-axis stage 826 moves alongy-axis rails 828 toward tape path assembly 118. At the same time, head808 rotates downward such that second edge 894 of pad 876 touches downon one side of tape 104, allowing seal 106 to make initial contact withtape 104 (shown in FIG. 43A). Y-axis stage 826 continues to advancealong rails 828 in synchronized movement with the rotation of head 808.Head 808 rocks from second edge 894 to first edge 892 and then fromsecond edge 894 to first edge 892 a first time as y-axis stage 826advances and retracts, respectively, along y-axis rails 828. Thisrocking movement applies pressure to seal 106 and tape 104 to press seal106 onto tape 104. In this embodiment, if 15 or more pounds of pressureper square inch is applied by head 808 to tape 104, pressure sensitiveadhesive on seal 106 can be activated. In an alternate embodiment, theamount of pressure required is dependent on the pressure sensitiveadhesive being used. While head 808 moves across tape 104 the firsttime, vacuum chambers 890 are deactivated and seal 106 is transferred totape 104. In an alternative embodiment, vacuum chambers 890 are notdeactivated and seal 106 is still transferred to tape 104.

After seal 106 has been applied, y-axis stage 826 moves back alongy-axis rails 828, across tape 104, and actuator 812 drives x-axis stage822 along x-axis rails 824 slightly downstream or upstream in the xdirection. This motion shifts head 808 slightly downstream or upstreamfrom where seal 106 was applied, and allows y-axis stage 826 to againmove forward across tape 104 in synchronized movement with the rotationof head 808. Head 808 rocks from second edge 894 to first edge 892 andthen from second edge 894 to first edge 892 a second time as y-axisstage 826 advances and retracts, respectively, along rails 828. Thissecond rocking movement ensures the pressure sensitive adhesive isactivated over the entire surface of seal 106, including where vacuumholes 878 were placed relative to tape 104 and seal 106 during the firstrocking movement of head 808.

Thermal Unit and Heated Pressure Chamber

FIG. 44 is an isometric view of tape path assembly 118 that runs throughinstrument 100. Tape path assembly 118 includes first position 130,second position 132, third position 134, and fourth position 136. Alsoshown in FIG. 45 are tape 104, thermal unit 210, and heated pressurechamber 212.

Tape 104 includes a matrix of wells that can contain a biological sampleand reagent mixture. Tape 104 is fed into tape path assembly 118 andthen advances to first position 130. Positioned beneath first position130 is a tape cutter. The tape cutter can be actuated upward to cut tape104 if desired. Tape 104 can also advance along tape path assembly 118without being cut. Tape 104 advances from first position 130 to secondposition 132 along tape path assembly 118. In section position 132, thebiological sample and reagent mixture are dispensed into tape 104 withdispensing assembly 114 (not shown). The biological sample and reagentmixture mix together in the matrix of wells of tape 104 to create thebiological sample and reagent mixture. The biological sample and reagentmixture in tape 104 can be heated or cooled at second position 132 witha thermal unit that is positioned underneath second position 132. Seal106 can be also be placed over the matrix of wells of tape 104 to sealthe biological sample and reagent mixture in the matrix of wells whentape 104 is in second position 132. After dispensing and sealing, tape104 advances to third position 134. The biological sample and reagentmixture in tape 104 can be heated or cooled at third position 134 with athermal unit that is positioned underneath third position 134. Tape 104can wait at third position 134 until instrument 100 is prepared toanalyze the biological sample and reagent mixture in tape 104.

When instrument 100 is ready to amplify and analyze the biologicalsample and reagent mixture, tape 104 can advance to fourth position 136.Positioned beneath fourth position 136 is thermal unit 210 to controlthe temperature of the biological sample and reagent mixture in tape104. Positioned above fourth position 136 is heated pressure chamber 212to create a constant pressure across the top of tape 104. Thermal unit210 can be used to heat the biological sample and reagent mixture at aconstant temperature or cycle the biological sample and reagent mixturethrough multiple temperatures. Heated pressure chamber 212 can be sealedoff from the ambient air surrounding heated pressure chamber 212. Heatedpressure chamber 212 pressurizes and heats the area above fourthposition 136 so that the biological sample and reagent mixture in tape104 can be analyzed. Heated pressure chamber 212 further heats thebiological sample and reagent mixture and prevents condensation on seal106 covering the matrix of wells of tape 104 to ensure accurateanalysis. Either after or during heating, the biological sample andreagent mixture can be analyzed using a camera that is positioned abovefourth position 136.

Thermal unit 210 and heated pressure chamber 212 can also be utilized toimprove application and adhesion of a bottom side of seal 106 to a topside of tape 104 when tape 104 is to be used external to instrument 100.In one embodiment, this use of tape 104 can be thermal cycling of tape104 in a water bath. To improve application and adhesion of seal 106 ontape 104, tape 104 is advanced into fourth position 136, thermal unit210 is raised, heat and pressure are applied to an enclosed space ofheated pressure chamber 212, and an amount of time is allowed to elapse.In one embodiment, this time may be 60 seconds. In other embodiments,any reasonable amount of time may be used. When the operation iscomplete, thermal unit 210 is lowered, heated pressure chamber 212 israised, and tape 104 can be advanced for use external to instrument 100.

In this embodiment, adhesive between seal 106 and tape 104 is optimallyapplied at greater than room temperature. Also, the force applied toseal 106 by pressurizing the enclosed space, and thereby pressing seal106 against tape 104, is uniform across the entirety of seal 106. Thisforce helps ensure that a bottom side of seal 106 of tape 104 that isnot immediately over a well of tape 104 is in contact with a top side oftape 104. Thus, applying heat and pressure over time can greatly improvethe adhesion of seal 106 to tape 104.

FIG. 45A is a perspective view of thermal unit 210 and heated pressurechamber 212, with heated pressure chamber 212 in a closed position. FIG.45B is a perspective view of thermal unit 210 and heated pressurechamber 212, with heated pressure chamber 212 in an open position. FIG.45C is an exploded view of thermal unit 210 and heated pressure chamber212. Also shown in FIG. 45C are tape 104 and seal 106. FIG. 45D is anexploded view of thermal unit 210. FIG. 45E is an exploded view ofheated pressure chamber 212.

Thermal unit 210 is used to control the temperature of the biologicalsample and reagent mixture in the matrix of wells of tape 104. Tape 104can be positioned on a top side of thermal unit 210. Thermal unit 210includes cavities that are configured to receive the matrix of wells oftape 104. The cavities of thermal unit 210 are slightly smaller than orthe same size as the wells of tape 104 in order to form a solid contactbetween the interior surface of the cavities of thermal unit 210 and theexterior surface of the wells of tape 104. Thermal unit 210 can be usedto heat and cool the biological sample and reagent mixture in tape 104.Thermal unit 210 can heat the biological sample and reagent mixture at aconstant temperature or thermal unit 210 can cycle the biological sampleand reagent mixture through multiple temperatures.

Positioned above thermal unit 210 and tape 104 is heated pressurechamber 212. When thermal unit 210 heats a mixture in tape 104, vaporpressure in the wells of tape 104 may cause seal 106 to delaminate fromtape 104. Heated pressure chamber 212 pressurizes the space above seal106 of tape 104 to create a force that pushes against seal 106. Thepressure keeps seal 106 in contact with tape 104 and also presses thematrix of wells of tape 104 into the cavities of thermal unit 210 inorder to provide better heat transfer between thermal unit 210 and thebiological sample and reagent mixture in the matrix of wells of tape104. Heated pressure chamber 212 also heats the area above tape 104 toprevent condensation from forming on seal 106 so that accurate detectioncan occur. Either during or after the biological sample and reagentmixture are heated with thermal unit 210, a camera, such as a CCDcamera, positioned above heated pressure chamber 212 can analyze thebiological sample and reagent mixture in the matrix of wells in tape104.

Thermal unit 210 includes first housing portion 1002, second housingportion 1004, gasket 1006, mounting feature 1008, inlet ports 1010,outlet ports 1012, recess 1014, thermal block 1020, wells 1022, fluidpath 1052 (not shown in FIGS. 45A-45E), and fluid path 1054 (not shownin FIGS. 45A-45E). Thermal block 1020 includes first plate 1030, firstsheet 1032, second plate 1034, second sheet 1036, thermoelectric modules(TEMs) 1038, heat transfer compound 1040 (not shown in FIGS. 45A-45E),and temperature sensor 1042. Thermal unit 210 will be discussed in moredetail below in FIGS. 46A-49.

Stationary frame 990 is connected to tape path assembly 118. Movableframe 992 is connected to stationary frame 990 with hinge pins 994.Stationary frame 990 is connected to actuator 996 with vertical mounts998. Actuator 996 is connected to movable frame 992 with pin 1000.Interface bracket 1058 of heated pressure chamber 212 connects heatedpressure chamber 212 to movable frame 992. In the embodiment shown,actuator 996 is an air cylinder. In alternative embodiments, actuator996 can be another type of actuator, such as a pneumatic, hydraulic,solenoid, or electromagnetic actuator. Actuator 996 moves heatedpressure chamber 212 from a closed position (FIG. 45A) to an openposition (FIG. 45B) by rotating movable frame 992 around hinge pins 994.

Heated pressure chamber 212 includes interface bracket 1058, clamp 1060,housing 1062, bolts 1064, glass cover plate 1066, gasket 1068, gasket1070, insulator plate 1071, gasket 1072, gasket 1073, enclosed space1074 (not shown in FIGS. 45A-45B), heater plenum 1076 with airdistribution orifices 1077, heating element 1078, compressed air fitting1080, electrical connection 1082 (not shown in FIGS. 45A-45E), mask 1084(not shown in FIGS. 45A-45E), air pump fitting 1086, air pump fitting1087, air pump fitting 1088, air pump fitting 1089, air pump fitting1090, air pump fitting 1092, air pump 1094 (not shown in FIGS. 45A-45E),compressed air source 1096 (not shown in FIGS. 45A-45E), and temperaturesensor 1098 (not shown in FIGS. 45A-45E). Heated pressure chamber 212will be discussed in more detail below in FIGS. 50-52.

FIG. 46A is a perspective view of thermal unit 210. FIG. 46B is aperspective view of the bottom of thermal unit 210. FIG. 46C is a topview of thermal unit 210. FIG. 46D is an isometric view of an array oftape 104 on thermal unit 210. Thermal unit 210 includes first housingportion 1002, second housing portion 1004, gasket 1006, mounting feature1008, inlet ports 1010, outlet ports 1012, recess 1014, thermal block1020, and cavities 1022. Also shown in FIG. 46D is tape 104.

Thermal unit 210 is positioned along tape path assembly 118 ininstrument 100. Thermal unit 210 includes first housing portion 1002positioned above second housing portion 1004. Gasket 1006 is positionedbetween first housing portion 1002 and second housing portion 1004.Mounting feature 1008 is positioned around second housing portion 1004.Second housing portion 1004 includes mounting feature 1008, which can beused to mount thermal unit 210 in tape path assembly 118.

Thermal unit 210 also includes two inlet ports 1010 and two outlet ports1012. Inlet ports 1010 are positioned on a first end of thermal unit 210and can receive a fluid. That fluid can flow through a thermalmanagement system in first housing portion 1002. Outlet ports 1012 arepositioned on a second end of thermal unit 210 and can expel the fluidfrom the thermal management system in first housing portion 1002.Thermal unit 210 further includes recess 1014. Recess 1014 is positionedon a first side of first housing portion 1002 and extends into firsthousing portion 1002.

Thermal unit 210 further includes thermal block 1020. Thermal block 1020is positioned in recess 1014 and does not directly contact first housingportion 1002. Thermal block 1020 includes a heat pump that can be usedto heat or cool a biological sample and reagent mixture in a matrix ofwells of tape 104. Thermal block 1020 further includes cavities 1022.Cavities 1022 are configured to receive the matrix of wells of tape 104.Each cavity 1022 is sized slightly smaller than or the same as the sizeof one well on tape 104. This allows an exterior surface of each of thewells in the matrix of wells of tape 104 to form a solid contact with aninterior surface of one cavity 1022. Forming a solid contact between aninterior surface of each cavity 1022 and an exterior surface of one ofthe wells in the matrix of wells of tape 104 provides for better heattransfer. The solid contact between each cavity 1022 on thermal block1020 with a well in the matrix of wells of tape 104 provides better heattransfer between the heat pump in thermal block 1020 and the biologicalsample and reagent mixture in the matrix of wells of tape 104. Betterheat transfer allows for more precise control of the temperature of thebiological sample and reagent mixture in the matrix of wells of tape104.

As seen in the embodiment shown in FIGS. 46A-46C, thermal unit 210includes 768 cavities 1022. The 768 cavities 1022 include two matricesof 384 cavities 1022 that are arranged in an offset and interlacedpattern. This allows cavities 1022 to receive tape 104 that has a matrixof 768 wells. In alternate embodiments, thermal unit 210 can includesany number of cavities 1022 and cavities 1022 can be arranged in anysuitable pattern.

FIG. 47A is a cross-sectional side view of thermal unit 210. FIG. 47B isa cut-away cross-sectional side view of thermal unit 210. FIG. 47C is aschematic view of a cross-section of thermal unit 210. Thermal unit 210includes first housing portion 1002, second housing portion 1004, gasket1006, mounting feature 1008, inlet ports 1010, outlet ports 1012, recess1014, thermal block 1020, and cavities 1022. Thermal block 1020 includesfirst plate 1030, first sheet 1032, second plate 1034, second sheet1036, TEMs 1038, and heat transfer compound 1040.

Thermal unit 210 includes first housing portion 1002 that is connectedto second housing portion 1004 with gasket 1006. Mounting feature 1008is part of second housing portion 1004 and can be used to mount secondhousing portion 1004 in tape path assembly 118. Inlet ports 1010 areconnected to a first end of thermal unit 210 and outlet ports 1012 areconnected to a second end of thermal unit 210 so that a fluid can berouted through thermal unit 210. Recess 1014 is positioned on a firstside of first housing portion 1002. Thermal unit 210 further includesthermal block 1020 positioned in recess 1014 of first housing portion1002. Thermal block 1020 includes a plurality of cavities 1022 that areconfigured to receive a matrix of wells of tape 104.

Thermal block 1020 includes first plate 1030, first sheet 1032, secondplate 1034, second sheet 1036, TEMs 1038, and heat transfer compound1040. First plate 1030 is an aluminum plate that is configured to spreadheat throughout first plate 1030 in the embodiment shown. In alternateembodiments, first plate 1030 can be made out of any material that iscapable of transferring and spreading heat. First plate 1030 is between1 millimeter (0.039 inches) and 10 millimeters (0.394 inches) thick.More preferable, first plate 1030 is between 1 millimeter (0.039 inches)and 3 millimeters (0.118 inches) thick. First plate 1030 containscavities 1022 of thermal block 1020. Cavities 1022 are cavities thatextend a distance into first plate 1030.

A bottom side of first plate 1030 is attached to a top side of firstsheet 1032. A bottom side of first sheet 1032 is attached to a top sideof second plate 1034. In this embodiment, first sheet 1032 is apyrolytic graphite sheet that is used to attach and conduct heat betweenfirst plate 1030 and second plate 1034. In other embodiments, firstsheet 1032 can be a heat transfer compound or any other heat transfermedium.

Second plate 1034 is a copper plate that is configured to transfer heatin the embodiment shown. In alternate embodiments, second plate 1034 canbe made out of any material that is capable of transferring andspreading heat. Second plate 1034 is between 0.5 millimeters (0.019inches) and 5 millimeters (0.197 inches) thick. More preferably, secondplate 1034 is between 0.5 (0.019 inches) millimeters and 2 millimeters(0.079 inches) thick.

A bottom side of second plate 1034 is attached to a top side of secondsheet 1036. A bottom side of second sheet 1036 is attached to a top sideof TEMs 1038. In this embodiment, second sheet 1036 is a pyrolyticgraphite sheet that is used to attach and conduct heat between secondplate 1034 and TEMs 1038. In other embodiments, second sheet 1036 can bea heat transfer paste or any other suitable heat transfer medium.

TEMs 1038 are positioned below first plate 1030 and second plate 1034.TEMs 1038 make up the heat pump of thermal block 1020. TEMs 1038generate heat that can be transferred and spread through second plate1034 and first plate 1030 into a biological sample and reagent mixtureheld in a matrix of wells in tape 104. In alternate embodiments, anysuitable heat pump can be used in place of TEMs 1038.

Heat transfer compound 1040 is used to attach a bottom side of TEMs 1038to first housing portion 1002. A portion of a thermal management systemis positioned in a lower half of first housing portion 1002 beneath thecavity that holds thermal block 1020. The portion of the thermalmanagement system is used to exchange heat with TEMs 1038. In theembodiment shown, heat transfer compound 1040 is a silicon basedcompound used to improve heat transfer between the portion of thethermal management system and TEMs 1038. In alternate embodiments, heattransfer compound 1040 can be a pyrolytic graphite sheet or any othersuitable heat transfer medium.

Thermal unit 210 is advantageous, as it is compact system that iscapable of being placed within tape path assembly 118 in instrument 100.Further, the configuration of thermal unit 210 with multiple layers ofplates allows different materials to be used to ensure that the transferand spread of heat from TEMs 1038 through thermal block 1020 isefficient and effective. Using copper, which has a higher thermalconductivity than aluminum, for second plate 1034 allows heat from TEMs1038 to spread and transfer uniformly through second plate 1034 to firstplate 1030. Using aluminum, which has a lesser density than copper, forfirst plate 1030 increases the rate of temperature change in first plate1030 and second plate 1034 for the same amount of energy from TEMs 1038.Combined, the materials used in first plate 1030, first sheet 1032,second plate 1034, and second sheet 1036 ensure that heat is transferredand spread throughout first plate 1030 to rapidly and uniformly heat orcool the biological sample and reagent mixture in the matrix of wells oftape 104 positioned on thermal unit 210. Uniformly heating or coolingthe biological sample and reagent mixture is necessary to obtainconsistent and accurate results when analyzing the biological sample andreagent mixture. In this context, heating or cooling should beunderstood to be inclusive of thermal cycling.

FIG. 48 is a top plan see-through view of a top side of thermal unit210. Thermal unit 210 includes first housing portion 1002, thermal block1020, and cavities 1022. Thermal block 1020 includes TEMs 1038 andtemperature sensor 1042.

First housing portion 1002 of thermal unit 210 houses thermal block1020. Cavities 1022 are positioned on a top side of thermal block 1020and are configured to receive a matrix of wells of tape 104. Thermalblock 1020 includes TEMs 1038. In the embodiment shown in FIG. 48,thermal block 1020 includes six different TEMs 1038. In alternateembodiments, thermal block 1020 can include any number of TEMs 1038.Further, TEMs 1038 can be any heat source that is capable of heating andcooling a biological sample and a reagent.

TEMs 1038 are arranged to uniformly heat or cool thermal block 1020. Asseen in the embodiment shown in FIG. 48, three TEMs 1038 are positionedon a first side of thermal unit 210 and the remaining three TEMs 1038are positioned on a second side of thermal unit 210. Heat that isgenerated in TEMs 1038 can transfer through thermal block 1020 to heator cool a biological sample and reagent mixture in the matrix of wellsof tape 104 that are positioned in cavities 1022 of thermal unit 210.Temperature sensor 1042 measures the temperature of thermal unit block1020. In the embodiment shown, temperature sensor 1042 is a resistancetemperature detector that monitors the temperature of thermal block 1020and provides feedback to the control system of instrument 100 such thatthe control system either heats, cools, or maintains a set pointtemperature of thermal block 1020.

FIG. 49 is a bottom plan see-through view of thermal unit 210. Thermalunit 210 includes first housing portion 1002, fluid path 1052, and fluidpath 1054. Fluid path 1052 and fluid path 1054 are positioned in abottom half of first housing portion 1002.

Fluid path 1052 is a cavity that runs from a first end of thermal unit210 to a second end of thermal unit 210. Fluid path 1052 snakes back andforth between the first end and the second end of thermal unit 210 on afirst side of thermal unit 210. A fluid can run through fluid path 1052to exchange heat with thermal block 1020. Fluid flows through an inletport (see FIGS. 45A-45B) on a first end of thermal unit 210, throughfluid path 1052, and out of an outlet port (see FIGS. 45A-45B) on asecond end of thermal unit 210.

Fluid path 1054 is a cavity that runs from a first end of thermal unit210 to a second end of thermal unit 210. Fluid path 1054 snakes back andforth between the first end and the second end of thermal unit 210 on asecond side of thermal unit 210. A fluid can run through fluid path 1054to exchange heat with thermal block 1020. Fluid flows through an inletport (see FIGS. 45A-45B) on a first end of thermal unit 210, throughfluid path 1054, and out of an outlet port (see FIGS. 45A-45B) on asecond end of thermal unit 210.

Fluid path 1052 and fluid path 1054 are part of a thermal managementsystem in instrument 100. The thermal management system is a closed loopsystem and fluid that flows through fluid path 1052 and fluid path 1054flows through a radiator (not shown in FIG. 49) to be cooled or heatedas needed. That fluid can then flow through fluid path 1052 and fluidpath 1054 again to exchange heat with thermal unit 210. The thermalmanagement system is advantageous, as it is an efficient and compact wayto control the temperature of thermal block 1020 in thermal unit 210.

FIG. 50 is a cross-sectional view of tape 104 with seal 106 sealedbetween thermal unit 210 and heated pressure chamber 212. Heatedpressure chamber 212 includes interface bracket 1058, clamp 1060,housing 1062, bolts 1064, glass cover plate 1066, gasket 1068, gasket1070, insulator plate 1071, gasket 1072, gasket 1073, enclosed space1074, heater plenum 1076 with distribution orifices 1077, heatingelement 1078, compressed air fitting 1080, and multi-pin electricalconnector 1082 (seen in FIG. 51). Clamp 1060 can be made of aluminum andis connected to housing 1062 with bolts 1064. Housing 1062 can be a lowthermal conductivity thermoplastic polymer such as polyether etherketone (PEEK) such that housing 1062 does not absorb heat generatedwithin enclosed space 1074. In alternative embodiments, housing 1062 canbe any heat resistant material or material with low thermalconductivity.

Glass cover plate 1066 is clamped in between gasket 1068 and gasket1070.

Clamp 1060 holds glass cover plate 1066 in place so that glass coverplate 1066 does not move when pressure is applied to glass cover plate1066. Gasket 1068 creates a seal between glass cover plate 1066 andclamp 1060. Gasket 1070 creates a seal between glass cover plate 1066and housing 1062. Gaskets 1068 and 1070 prevent chipping and cracking ofglass cover plate 1066 and facilitate even pressure distribution acrossglass cover plate 1066. Gasket 1072 creates a seal between housing 1062and tape 104.

Clamp 1060, housing 1062, bolts 1064, glass cover plate 1066, gasket1068, gasket 1070, and gasket 1072 create enclosed space 1074. Enclosedspace 1074 is a sealed, enclosed space above tape 104 and seal 106 thatcan be heated and pressurized. Insulator plate 1071, gasket 1073, heaterplenum 1076, and heating element 1078 are located within enclosed space1074. Insulator plate 1071 insulates heating element 1078 and heaterplenum 1076, minimizing heat loss from enclosed space 1074. Heatingelement 1078 heats enclosed space 1074 to prevent condensation on seal106 in the wells of tape 104. Heater plenum 1076 includes airdistribution orifices 1077, which circulate air within enclosed space1074 to facilitate uniform heat distribution within enclosed space 1074.Gasket 1073 creates a seal between heater plenum 1076 and housing 1062.Heater plenum 1076 can be aluminum. In alternative embodiments, heaterplenum 1076 can be any other suitable material with high thermalconductivity, such as stainless steel. Compressed air fitting 1080 isattached to housing 1062 and can be connected to a compressed air sourceto provide compressed air for pressurizing enclosed space 1074.Multi-pin electrical connector 1082 is attached to housing 1062 andpowers heating element 1078.

In order to amplify and analyze a biological sample and reagent mixture,tape 104 with seal 106 is positioned between thermal unit 210 and heatedpressure chamber 212 such that a matrix of wells of tape 104 is alignedwith the matrix of wells of thermal unit 210. Thermal unit 210 is raisedand heated pressure chamber 212 is lowered such that tape 104 is pressedagainst gasket 1072 and the matrix of wells of tape 104 is pressed intothe matrix of wells of thermal unit 210. Heated pressure chamber 212 issealed by raising the lift to which thermal unit 210 is attached, whichin turn causes a top surface of first housing portion 1002 of thermalunit 210 to come into contact with a bottom surface of tape 104. Thispushes a top surface of tape 104 up against a bottom surface of gasket1072 of the heated pressure chamber 212. Compressed air is fed throughcompressed air fitting 1080 into enclosed space 1074 above tape 104 andseal 106. Compressed air pressurizes enclosed space 1074 to between 5psi and 20 psi. Heating element 1078 heats the air in enclosed space1074. Depending on the temperature of thermal unit 210 duringamplification, the air temperature within enclosed space 1074 may bebetween 70 and 120 degrees Celsius. Heater plenum 1076 with airdistribution orifices 1077 accelerates heating and facilitates uniformheat distribution within enclosed space 1074.

A desired pressure and temperature is maintained in enclosed space 1074while a biological sample and reagent mixture is amplified and detectedin the matrix of wells of tape 104. When amplification and detection iscomplete, thermal unit 210 is lowered, heated pressure chamber 212 israised, and tape 104 advances along tape path 118 such that a new matrixof wells of tape 104 is positioned between thermal unit 210 and heatedpressure chamber 212.

FIG. 51 is an isometric view of heated pressure chamber 212. Heatedpressure chamber 212 includes interface bracket 1058, clamp 1060,housing 1062, heater plenum 1076 with air distribution orifices 1077,glass cover plate 1066 with mask 1084, compressed air fitting 1080,multi-pin electrical connector 1082, and air pump fittings 1086. Airpump fittings 1086 can be connected to an air pump for pumping air intoand out of enclosed space 1074 to facilitate uniform temperaturedistribution within enclosed space 1074.

Glass cover plate 1066 with mask 1084 allows accurate detection of themixture in the matrix of wells of tape 104. Mask 1084 is two dots onglass cover plate 1066 and allows instrument 100 to recognize that anarray of tape 104 is present in thermal unit 210. Mask 1084 can beetched or printed onto a bottom surface of glass cover plate 1066. Glasscover plate 1066 can be a ten millimeter thick anti-reflective coatedglass cover plate to allow the camera to see the entire matrix of wellsduring detection.

FIG. 52 is a top view of heated pressure chamber 212. Heated pressurechamber 212 includes clamp 1060, bolts 1064, glass cover plate 1066 withmask 1084, heater plenum 1076 (shown in FIGS. 50-51), heating element1078 (shown in FIG. 50), compressed air fitting 1080, multi-pinelectrical connector 1082, air pump fitting 1086, air pump fitting 1087,air pump fitting 1088, air pump fitting 1089, air pump fitting 1090, andair pump fitting 1092, air pump 1094, compressed air source 1096, andtemperature sensor 1098. Compressed air source 1096 pumps compressed airinto enclosed space 1074 through compressed air fitting 1080 forpressurizing enclosed space 1074.

Air pump fitting 1086, air pump fitting 1087, air pump fitting 1088, airpump fitting 1089, air pump fitting 1090, and air pump fitting 1092 areconnected to air pump 1094, forming a closed circuit of air flow. Airflows out of air pump 1094, through air pump fittings 1086, 1087, 1088,and 1089, across enclosed space 1074, out of air pump fittings 1090 and1092, and back into air pump 1094. The closed circuit of air flow movesthe air at approximately four liters per minute within enclosed space1074 to facilitate uniform temperature distribution within enclosedspace 1074. In alternative embodiments, air can flow into any four ofair pump fittings 1086, 1087, 1088, 1089, 1090, and 1092 and out of anytwo of air pump fittings 1086, 1087, 1088, 1089, 1090, and 1092.

Heating element 1078 is embedded in a heat-tolerant media and connectedto heater plenum 1076 with an adhesive. In one embodiment, theheat-tolerant media can be a polyamide. In an alternative embodiment,the heat-tolerant media can be a silicone rubber media. Heating element1078 is connected to heater plenum 1076 with adhesive. The adhesivesticks to heater plenum 1076 and the heat-tolerant media in whichheating element 1078 is embedded. In one embodiment, heating element1078 can be a copper-based resistive heater, such as a copper alloyheater. In alternative embodiments, heating element 1078 is a heaterthat fits within the space constraints of enclosed space 1074. Heatingelement 1078 heats the air in enclosed space 1074 to a desiredtemperature and heater plenum 1076 absorbs and transfers the heat tofacilitate uniform temperature distribution within enclosed space 1074.

Multi-pin electrical connector 1082 provides power to heating element1078 and power to and sensor values from temperature sensor 1098 whilemaintaining a pressure-type connection to housing 1062. Temperaturesensor 1098 senses the temperature of heater plenum 1076 such that thetemperature within enclosed space 1074 can be controlled. In oneembodiment, heater plenum 1076 is maintained at 115 degrees Celsius suchthat the temperature in enclosed space 1074 is approximately 105 degreesCelsius. In alternative embodiments, heater plenum 1076 is maintained ata temperature such that the air temperature within enclosed space 1074is maintained at a desired temperature between 70 and 120 degreesCelsius.

Alternative Embodiments of the Overall Instrument

FIG. 53A is a schematic of instrument 100A. FIG. 53B is a schematic ofinstrument 100B. Instrument 100A and instrument 100B are alternativeembodiments of instrument 100 seen in FIGS. 1-52. Instrument 100Aincludes tape path assembly 118A, which includes tape cutting station1100, dispensing and sealing station 1102, waiting station 1104, and aplurality of amplification and detection stations 1106 (includingamplification and detection station 1106A, amplification and detectionstation 1106B, and amplification and detection station 1106C).Instrument 100B includes tape path assembly 118B, which includes tapecutting station 1110, dispensing and sealing station 1112, a pluralityof waiting stations 1114 (including waiting station 1114A and waitingstation 1114B), and a plurality of amplification and detection stations1116 (including amplification and detection station 1116A, amplificationand detection station 1116B, and amplification and detection station1116C).

Tape path assemblies 118A and 118B extend through instruments 100A and100B, respectively, and provide a path along which tape 104 having aplurality of wells can advance. Tape 104 moves through instruments 100Aand 100B from an entrance to an exit of tape path assemblies 118A and118B through the different stations on tape path assemblies 118A and118B.

Instrument 100A includes tape cutting station 1100 that is positionedbetween an entrance of tape path assembly 118A and dispensing andsealing station 1102; dispensing and sealing station 1102 is positionedbetween tape cutting station 1100 and waiting station 1104; waitingstation 1104 is positioned between dispensing and sealing station 1102and the plurality of amplification and detections stations 1106; and theplurality of amplification and detection stations 1106 are positionedbetween waiting station 1104 and an exit of tape path assembly 118A. Theplurality of amplification and detection stations 1106 include threedifferent amplification and detection stations in the embodiment shownin FIG. 53A, but can include any number of amplification and detectionstations in alternate embodiments.

Amplification and detection stations 1106 are arranged in parallel withone another in instrument 100A. Tape 104 that enters instrument 100A canbe cut into a first tape segment with a single array of wells at tapecutting station 1100. The first tape segment can then move to dispensingand sealing station 1102, where a biological sample and a reagent can bedispensed into the first tape segment to form a biological sample andreagent mixture. The biological sample and reagent mixture can then besealed in the first tape segment at dispensing and sealing station 1102.Further, the first tape segment can be cooled to prevent the biologicalsample and reagent mixture from undergoing a chemical reaction or heatedto incubate the biological sample and reagent mixture at dispensing andsealing station 1102. The first tape segment can then move to waitingstation 1104 where the first tape segment can again be cooled to preventthe biological sample and reagent mixture from undergoing a chemicalreaction or heated to incubate the biological sample and reagentmixture.

From waiting station 1104, the first tape segment can be routed toamplification and detection station 1106A, amplification and detectionstation 1106B, or amplification and detection station 1106C. At any ofthe plurality of amplification and detection stations 1106, thebiological sample and reagent mixture can undergo thermal cycling or beheated at a constant temperature. The biological sample and reagentmixture can also be analyzed at amplification and detection stations1106.

After first tape segment has moved from dispensing and sealing station1102 to waiting station 1104, a second tape segment can be cut from tape104 and moved to dispensing and sealing station 1102. The second tapesegment will undergo the same processing as the first tape segment butit can be moved to a different one of the plurality of amplification anddetection stations 1106. Further, a third tape segment can be cut fromtape 104 and moved to dispensing and sealing station 1102. The thirdtape segment will undergo the same processing as the first and secondtape segments and moved to the final of the plurality of amplificationand detection stations 1106. Having a plurality of amplification anddetection stations 1106 allows instrument 100A to analyze multiplearrays of tape 104 at the same time. Amplification and detectionstations 1106 can begin the processing of tape 104 when tape 104 reacheseach amplification and detection station 1106, or amplification anddetection stations 1106 can be run at the same time. In an alternateembodiment, waiting station 1104 can be eliminated and the tape segmentscan pass from dispensing and sealing station 1102 to one of theplurality of amplification and detection stations 1106.

Each of the plurality of amplification and detection stations 1106 caninclude the same means for analysis or different means for analysis. Forexample, amplification and detection stations 1106 can all analyze thebiological sample and reagent mixture using polymerize chain reactionanalysis. Alternatively, amplification and detection station 1106A cananalyze the biological sample and reagent mixture using polymerize chainreaction analysis, amplification and detection station 1106B can analyzethe biological sample and reagent mixture using melt curve analysis, andamplification and detection station 1106C can analyze the biologicalsample and reagent mixture using isothermal amplification analysis.Having different means of analysis at each amplification and detectionstation 1106 allows a sample to undergo different analysis at the sametime.

Instrument 100B includes tape cutting station 1110 that is positionedbetween an entrance of tape path assembly 118B and dispensing andsealing station 1112; dispensing and sealing station 1112 is positionedbetween tape cutting station 1110 and waiting station 1114A; waitingstation 1114A is positioned between dispending and sealing station 1112and waiting station 1114B; waiting station 1114B is positioned betweenwaiting station 1114A and amplification and detection station 1116A;amplification and detection station 1116A is positioned between waitingstation 1114B and amplification and detection station 1116B;amplification and detection station 1116B is positioned betweenamplification and detection station 1116A and amplification anddetection station 1116C; and amplification and detection station 1116Cis positioned between amplification and detection stations 1116B and anexit of tape path assembly 118A. The plurality of amplification anddetection stations 1116 include three different amplification anddetection stations in the embodiment shown in FIG. 53B, but can includeany number of amplification and detection stations in alternateembodiments.

Amplification and detection stations 1116 are arranged in series withone another in instrument 100B. Tape 104 that enters instrument 100B canbe cut into a first tape segment with a single array of wells at tapecutting station 1100 or tape 104 can advance as a web through tapecutting station 1110 without being cut. A first array of tape 104 canthen move to dispensing and sealing station 1112, where a biologicalsample and a reagent can be dispensed into the first array of tape 104to form a biological sample and reagent mixture. The biological sampleand reagent mixture can be then be sealed in the first array of tape 104at dispensing and sealing station 1112. Further, the first array of tape104 can be cooled to prevent the biological sample and reagent mixturefrom undergoing a chemical reaction or heated to incubate the biologicalsample and reagent mixture at dispensing and sealing station 1112. Thefirst array of tape 104 can then move to waiting station 1114A where thefirst array of tape 104 can again be cooled to prevent the biologicalsample and reagent mixture from undergoing a chemical reaction or heatedto incubate the biological sample and reagent mixture.

When the first array of tape 104 advances to waiting station 1114A, asecond array of tape 104 can move to dispensing and sealing station1112. The second array of tape 104 can then undergo the same processingas the first array of tape 104 at dispensing and sealing station 1112.After this, the first array of tape 104 can move to waiting station1114B and the second array of tape 104 can move to waiting station1114A. Both waiting stations 1114A and 1114B can cool or heat thebiological sample and reagent mixture. A third array of tape 104 canthen move to dispensing and sealing station 1112. The third array oftape 104 can then undergo the same processing as the first array of tape104 at dispensing and sealing station 1112. At this point, tape 104 canmove through instrument 100B so that the first array of tape 104 ispositioned in amplification and detection station 1116C, the secondarray of tape 104 is positioned in amplification and detection station1116B, and the third array of tape 104 is positioned in amplificationand detection station 1116C. At any of the plurality of amplificationand detection stations 1116, the biological sample and reagent mixturecan undergo thermal cycling or be heated at a constant temperature. Thebiological sample and reagent mixture can also be analyzed atamplification and detection stations 1116. Having a plurality ofamplification and detection stations 1116 allows instrument 100B toanalyze multiple arrays at a single time. In an alternate embodiment,waiting stations 1114A and 1114B can be eliminated and tape 104 can movefrom dispensing and sealing station 1112 to the plurality ofamplification and detection stations 1116.

Each of the plurality of amplification and detection stations 1116 caninclude the same means for analysis or different means for analysis. Forexample, amplification and detection stations 1116 can all analyze thebiological sample and reagent mixture using polymerize chain reactionanalysis. Alternatively, amplification and detection station 1116A cananalyze the biological sample and reagent mixture using polymerize chainreaction analysis, amplification and detection station 1116B can analyzethe biological sample and reagent mixture using melt curve analysis, andamplification and detection station 1116C can analyze the biologicalsample and reagent mixture using isothermal amplification analysis.

Instrument 100A and instrument 100B are example alternate embodiments ofinstrument 100. It is appreciated that there can be any number ofalternate embodiments of instrument 100. For example, instrument 100 caninclude any number of amplification and detection stations arranged inseries, parallel, or both. Further, instrument 100 could include anynumber of dispensing stations arranged in series, parallel, or both.Instrument 100 can also include any number of waiting stations or nowaiting stations. Additionally, instrument 100 could also include anynumber of tape path assemblies. Having different means of analysis ateach amplification and detection station 1116 allows a sample to undergodifferent analysis at the same time.

The preceding description is a non-exclusive description of possibleembodiments of the present disclosure. It is contemplated that theelements disclosed can be combined in any manner. The instrumentdescribed can optionally include, additionally and/or alternatively, anyone or more of the features, configurations and/or components describedin the preceding description.

While the invention has been described with reference to an exemplaryembodiment(s), it will be understood by those skilled in the art thatvarious changes may be made and equivalents may be substituted forelements thereof without departing from the scope of the invention. Inaddition, many modifications may be made to adapt a particular situationor material to the teachings of the invention without departing from theessential scope thereof. Therefore, it is intended that the inventionnot be limited to the particular embodiment(s) disclosed, but that theinvention will include all embodiments falling within the scope of theappended claims.

The invention claimed is:
 1. An instrument for processing a biologicalsample, the instrument comprising: a dispensing assembly configured andarranged for aspirating and dispensing the biological sample and areagent into a matrix of wells of a tape to form a biological sample andreagent mixture; a sealing assembly configured and arranged for sealingthe biological sample and reagent mixture in the tape; an amplificationand detection assembly configured and arranged for detecting a signalfrom the biological sample and reagent mixture in the matrix of wells inthe tape, wherein the amplification and detection assembly includes: athermal unit configured and arranged to control the temperature of thebiological sample and reagent mixture in the matrix of wells of thetape, the thermal unit comprising a plurality of cavities configured toreceive respective wells of the matrix of wells, each cavity sized suchthat an exterior surface of a well forms a solid contact with aninterior surface of the cavity; and a pressure chamber mounted on thethermal unit to pressurize an area over the tape; and a tape pathassembly configured and arranged to advance the tape with the matrix ofwells between the dispensing assembly, sealing assembly andamplification and detection assembly.
 2. The instrument of claim 1,further comprising an analytics system to analyze the signal that isdetected from the biological sample and reagent mixture by theamplification and detection assembly.
 3. The instrument of claim 1,wherein the thermal unit is configured to control the temperature of thebiological sample and reagent mixture in the matrix of wells of the tapefor enabling isothermal amplification and polymerase chain reaction. 4.The instrument of claim 1, wherein the thermal unit includes: a heatpump: a first layer comprising the plurality of cavities configured toreceive the respective wells of the matrix of wells; and a second layerpositions between the heat pump and first layer such that heat can beexchanged between the heat pump and the biological sample and reagentmixture in the matrix of wells through the first and second layers. 5.The instrument of claim 1, further comprising the tape with the matrixof wells, wherein the matrix of wells includes a first matrix of wellsinterlaced with a second matrix of wells in an offset pattern.
 6. Theinstrument of claim 1, wherein the tape path assembly defines a tapepath along which the tape is advanced between the dispensing assembly,sealing assembly and amplification and detection assembly.
 7. Theinstrument of claim 1, further comprising a plate rack configured tohold one or more plates containing the biological sample or the reagentto be aspirated and dispensed.
 8. The instrument of claim 7, furthercomprising a plate stacker configured to lift a plate out of the platerack.
 9. The instrument of claim 8, further comprising a plate shuttlewith a platform on which the plate stacker can place the plate from theplate rack, the plate shuttle configured to position the platform foraspirating or dispensing.
 10. The instrument of claim 1, furthercomprising at least one wash assembly configured and arranged to washportions of the dispensing assembly.
 11. The instrument of claim 6,wherein the tape path assembly comprises a drive mechanism configuredand arranged to automatically advance the tape along the tape path. 12.The instrument of claim 6, wherein the tape path assembly furthercomprises a tape infeed and tape cutter positioned adjacent a first endof the tape path.
 13. The instrument of claim 1, wherein the pressurechamber comprises a heating element.
 14. The instrument of claim 4,wherein the first layer is an aluminum layer and the second layer is acopper layer.
 15. An instrument for processing a biological sample, theinstrument comprising: a dispensing assembly configured and arranged foraspirating and dispensing fluid into one or more wells of a tape; asealing assembly configured and arranged for sealing the one or morewells; an amplification and detection assembly configured and arrangedfor detecting a signal from the one or more wells, wherein theamplification and detection assembly includes: a thermal unit configuredand arranged to control the temperature of content in the one or morewells of the tape, the thermal unit comprising a plurality of cavitiesconfigured to receive respective wells of the tape, each cavity sizedsuch that an exterior surface of a well forms a solid contact with aninterior surface of the cavity; and a pressure chamber mounted on thethermal unit to pressurize an area over the tape, a tape path assemblyconfigured to advance the tape between the dispensing assembly, sealingassembly and amplification and detection assembly; and at least one washassembly configured and arranged to wash portions of the dispensingassembly.
 16. The instrument of claim 15, further comprising the tapewith the wells, wherein the wells include a first matrix of wellsinterlaced with a second matrix of wells in an offset pattern.
 17. Theinstrument of claim 15, further comprising: a plate rack configured tohold one or more plates containing the fluid to be aspirated anddispensed; a plate stacker configured to lift a plate out of the platerack; and a plate shuttle including a platform on which the platestacker can place the plate from the plate rack, the plate shuttleconfigured to position the platform for aspirating or dispensing.